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The therapeutic potential of suppressing polypyrimidine tract-binding protein 1 (Ptbp1) messenger RNA by viral transduction in a post-stroke dementia mouse model has not yet been examined. In this study, 3 days after cerebral ischemia, we injected a viral vector cocktail containing adeno-associated virus (AAV)-pGFAP-mCherry and AAV-pGFAP-CasRx (control vector) or a cocktail of AAV-pGFAP-mCherry and AAV-pGFAP-CasRx-SgRNA-(Ptbp1) (1:5, 1.0 × 10 11 viral genomes) into post-stroke mice via the tail vein. We observed new mCherry/NeuN double-positive neuron-like cells in the hippocampus 56 days after cerebral ischemia. A portion of mCherry/GFAP double-positive astrocyte-like glia could have been converted into new mCherry/NeuN double-positive neuron-like cells with morphological changes. The new neuronal cells integrated into the dentate gyrus and recognition memory was significantly ameliorated. These results demonstrated that the in vivo conversion of hippocampal astrocyte-like glia into functional new neurons by the suppression of Ptbp1 might be a therapeutic strategy for post-stroke dementia., (© 2024. The Author(s).)

Ischemic stroke (IS) is a severe cerebrovascular disease with high disability and mortality rates, where the inflammatory response is crucial to its progression and prognosis. Efferocytosis, the prompt removal of dead cells, can reduce excessive inflammation after IS injury. While electroacupuncture (EA) has been shown to decrease inflammation post-ischemia/reperfusion (I/R), its link to efferocytosis is unclear. Our research identified ATP-binding cassette transporter A1 (Abca1) as a key regulator of the engulfment process of efferocytosis after IS by analyzing public datasets and validating findings in a mouse model, revealing its close ties to IS progression. We demonstrated that EA can reduce neuronal cell death and excessive inflammation caused by I/R. Furthermore, EA treatment increased Abca1 expression, prevented microglia activation, promoted M2 microglia polarization, and enhanced their ability to phagocytose injured neurons in I/R mice. This suggests that EA's modulation of efferocytosis could be a potential mechanism for reducing cerebral I/R injury, making regulators of efferocytosis steps a promising therapeutic target for EA benefits., (© 2024. The Author(s).)

Background: Large vessel occlusion acute ischemic stroke prognosis improved following the 2015 endovascular therapy (EVT) trials. Blood-based biomarkers may improve outcome prediction. We aimed to assess plasma brain-derived tau (BD-Tau) performance in predicting post-EVT large vessel occlusion acute ischemic stroke outcomes., Methods: We included 2 temporally independent prospective cohorts of anterior circulation in patients with large vessel occlusion acute ischemic stroke who successfully recanalized post-EVT. We measured plasma BD-Tau, GFAP (glial-fibrillary-acidic-protein), NfL (neurofilament-light-chain), and total-Tau upon admission, immediately, 24 hours, and 72 hours post-EVT. Twenty-four-hour neuroimaging and 90-day functional outcomes were independently assessed using the Alberta Stroke Program Early Computed Tomography Score (good outcome: >7 or unchanged) and the modified Rankin Scale (favorable outcome <3 or unchanged), respectively. Based on the first cohort (derivation), we built a multivariable logistic regression model to predict a 90-day functional outcome. Model results were evaluated using the second cohort (evaluation)., Results: In the derivation cohort (n=78, mean age=72.9 years, 50% women), 62% of patients had a good 24-hour neuroimaging outcome, and 45% had a favorable 90-day functional outcome. GFAP admission-to-EVT rate-of-change was the best predictor for early neuroimaging outcome but not for 90-day functional outcome. At admission, BD-Tau levels presented the highest discriminative performance for 90-day functional outcomes (area under the curve, 0.76 [95% CI, 0.65-0.87]; P <0.001). The model incorporating age, admission BD-Tau, and 24-hour Alberta Stroke Program Early Computed Tomography Score achieved excellent discrimination of 90-day functional outcome (area under the curve, 0.89 [95% CI, 0.82-0.97]; P <0.001). The score's predictive performance was maintained in the evaluation cohort (n=66; area under the curve, 0.82 [95% CI, 0.71-0.92]; P <0.001)., Conclusions: Admission plasma BD-Tau accurately predicted 90-day functional outcomes in patients with large vessel occlusion acute ischemic stroke after successful EVT. The proposed model may predict functional outcomes using objective measures, minimizing human-related biases and serving as a simplified prognostic tool for AIS., Competing Interests: Dr Maia reports compensation from Alnylam Pharmaceuticals and Bristol-Myers Squibb Company for consultant services. Dr Blennow reports compensation from Eli LIlly, EISAI INC, and F. Hoffmann-La Roche for consultant services. Dr Karikari reports grants from Vetenskapsrådet; a patent issued for Use of a ps396 assay to diagnose tauopathies https://patents.google.com/patent/WO2020193500A1/en; and grants from National Institutes of Health. Dr Zetterberg has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, and given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, which is a part of the GU Ventures Incubator Program (outside submitted work). N.L. Knuth reports a patent on the use of BD-Tau.

We have previously reported that the expression of miR-34c-5p was up-regulated during acupuncture treatment in the setting of a cerebral ischemia/reperfusion injury (CIRI), indicating that miR-34c-5p plays an important role in healing from a CIRI-induced brain injury. This study sought to evaluate the effects of acupuncture on miR-34c-5p expression and autophagy in the forward and reverse directions using a rat focal cerebral ischemia/reperfusion model. After 120 minutes of middle cerebral artery occlusion and reperfusion, rats were treated with acupuncture at the "Dazhui" (DU20), "Baihui" (DU26) and "Renzhong" (DU14) points. Neurologic function deficit score, cerebral infarct area ratio, neuronal apoptosis and miR-34c-5p expression were evaluated 72 hr after treatment. The autophagy agonist RAPA and the antagonist 3MA were used to evaluate the neuro protective effects of autophagy-mediated acupuncture. We found that acupuncture treatment improved autophagy in the brain tissue of CIRI rats. Acupuncture reversed the negative effects of 3MA on CIRI, and acupuncture combined with RAPA further enhanced autophagy. We also found that acupuncture could increase miR-34c-5p expression in hippocampal neurons after ischemia/reperfusion. Acupuncture and a miR-34c agomir were able to enhance autophagy, improve neurologic deficits, and reduce the cerebral infarct area ratio and apoptosis rate by promoting the expression of miR-34c-5p. Silencing miR-34c resulted in a significantly reduced activating effect of acupuncture on autophagy and increased apoptosis, neurologic deficit symptoms, and cerebral infarct area ratio. This confirms that acupuncture can upregulate miR-34c-5p expression, which is beneficial in the treatment of CIRI., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Remote ischemic post-conditioning (RIPostC) can reduce cerebral ischemia reperfusion injury (IRI) by inducing endogenous protective effects, the distal limb ischemia post-treatment and in situ ischemia post-treatment were classified according to the site of intervention. And in the process of clinical application distal limb ischemia post-treatment is more widely used and more conducive to clinical translation. Therefore, in this paper, we review the mechanism of action and clinical application of RIPostC in cerebral ischemia, hoping to provide reference help for future experimental directions and clinical translation., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: All work was performed at Oregon Health & Science University and the Department of Neurology at Cedars-Sinai Medical Center. Dr Christy participates in clinical trials in pediatric migraine with Biohaven, Abbvie, and Eli Lilly; and in pediatric multiple sclerosis with Novartis. She has served as a consultant for Azurity pharmaceuticals. She receives a stipend for her role as deputy editor of the Journal of Child Neurology. Dr Simpkins receives funding from the National Institute of Aging (3U54AG065141-04S1).

Ischemic stroke (IS) is a leading cause of death and disability worldwide. Tissue plasminogen activator (tPA) administration and mechanical thrombectomy are the main treatments but have a narrow time window. Mesenchymal stem cells (MSCs), which are easily scalable in vitro and lack ethical concerns, possess the potential to differentiate into various types of cells and secrete a great number of growth factors for neuroprotection and regeneration. Moreover, MSCs have low immunogenicity and tumorigenic properties, showing safety and preliminary efficacy both in preclinical studies and clinical trials of IS. However, it is unlikely that MSC treatment alone will be sufficient to maximize recovery due to the low survival rate of transplanted cells and various mechanisms of ischemic brain damage in the different stages of IS. Preconditioning was used to facilitate the homing, survival, and secretion ability of the grafted MSCs in the ischemic region, while combination therapies are alternatives that can maximize the treatment effects, focusing on multiple therapeutic targets to promote stroke recovery. In this case, the combination therapy can yield a synergistic effect. In this review, we summarize the type of MSCs, preconditioning methods, and combined strategies as well as their therapeutic mechanism in the treatment of IS to accelerate the transformation from basic research to clinical application., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Competing interests: BCVC was a site principal investigator for the SELECT 2 trial (Trial of endovascular thrombectomy for large ischemic strokes). No other disclosures or competing interests declared by the remaining authors.

Ischemia and hypoxia activate astrocytes into reactive types A1 and A2, which play roles in damage and protection, respectively. However, the function and mechanism of A1 and A2 astrocyte exosomes are unknown. After astrocyte exosomes were injected into the lateral ventricle, infarct volume, damage to the blood-brain barrier (BBB), apoptosis and the expression of microglia-related proteins were measured. The dual luciferase reporter assay was used to detect the target genes of miR-628, and overexpressing A2-Exos overexpressed and knocked down miR-628 were constructed. qRT-PCR, western blotting and immunofluorescence staining were subsequently performed. A2-Exos obviously reduced the infarct volume, damage to the BBB and apoptosis and promoted M2 microglial polarization. RT-PCR showed that miR-628 was highly expressed in A2-Exos. Dual luciferase reporter assays revealed that NLRP3, S1PR3 and IRF5 are target genes of miR-628. After miR-628 was overexpressed or knocked down, the protective effects of A2-Exos increased or decreased, respectively. A2-Exos reduced pyroptosis and BBB damage and promoted M2 microglial polarization through the inhibition of NLRP3, S1PR3 and IRF5 via the delivery of miR-628. This study explored the mechanism of action of A2-Exos and provided new therapeutic targets and concepts for treating cerebral ischemia., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Neurological injuries can have numerous debilitating effects on functional status including sensorimotor deficits, cognitive impairment, and behavioral symptoms. Despite the disease burden, treatment options remain limited. Current pharmacological interventions are targeted at symptom management but are ineffective in reversing ischemic brain damage. Stem cell therapy for ischemic brain injury has shown promising preclinical and clinical results and has attracted attention as a potential therapeutic option. Various stem cell sources (embryonic, mesenchymal/bone marrow, and neural stem cells) have been investigated. This review provides an overview of the advances made in our understanding of the various types of stem cells and progress made in the use of these stem cells for the treatment of ischemic brain injuries. In particular, the use of stem cell therapy in global cerebral ischemia following cardiac arrest and in focal cerebral ischemia after ischemic stroke are discussed. The proposed mechanisms of stem cells' neuroprotective effects in animal models (rat/mice, pig/swine) and other clinical studies, different routes of administration (intravenous/intra-arterial/intracerebroventricular/intranasal/intraperitoneal/intracranial) and stem cell preconditioning are discussed. Much of the promising data on stem cell therapies after ischemic brain injury remains in the experimental stage and several limitations remain unsettled. Future investigation is needed to further assess the safety and efficacy and to overcome the remaining obstacles., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Stroke is the second leading cause of death worldwide and a leading cause of disability. The innate immune response occurs immediately after cerebral ischemia, resulting in adaptive immunity. More and more experimental evidence has proved that the immune response caused by cerebral ischemia plays an important role in early brain injury and later the recovery of brain injury. Innate immune cells and adaptive cells promote the occurrence of cerebral ischemic injury but also protect brain cells. A large number of studies have shown that cytokines and immune-related substances also have dual functions of promoting injury, reducing injury, or promoting injury recovery in the later stage of cerebral ischemia. They can be an important target for treating cerebral ischemic recovery. Therefore, this study discussed the immune cells, cytokines, and immune-related substances with dual roles in cerebral ischemia and summarized the therapeutic targets of cerebral ischemia. To explore more effective methods to treat cerebral ischemia, promote the recovery of brain function, and improve the prognosis of patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [HaitongWan reports financial support was provided by National Key R&D Projects of China. LiYu reports financial support was provided by Natural Science Foundation of Zhejiang Province. HaitongWan reports financial support was provided by National Natural Science Foundation of China. WeifengJin reports financial support was provided by Natural Science Foundation of Zhejiang Province. LiYu reports financial support was provided by China Postdoctoral Science Foundation. LiYu reports financial support was provided by Postdoctoral research projects merit-based funding in Zhejiang province (First-class funding). HaitongWan reports financial support was provided by Key R&D Program of Zhejiang. YuejiaHe reports financial support was provided by University-level student research fund of Zhejiang Chinese Medical University. YuejiaHe reports financial support was provided by Xinmiao talents Project of Zhejiang Province. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The overall safety and efficacy of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) in frail patients is not well delineated. This systematic review aims to summarize and compare outcomes in frail and non-frail patients who underwent MT for AIS., Methods: A systematic review of the literature was performed using PubMed, Ovid Medline, and Web of Science to identify studies with outcomes-related data for frail patients with MT-treated AIS. The recanalization rate, procedural complications, and clinical outcome at 90-day follow-up were collected., Results: In the four included studies there were 642 frail patients and 499 non-frail patients. Frail patients had reduced rates of good functional outcomes (29% vs 42%; χ 2 =22, p<0.01) and increased 90-day mortality (51% vs 25%; χ 2 =38, p<0.01) compared with non-frail patients., Conclusion: MT for treatment of AIS in frail patients may be associated with worse rates of morbidity and mortality along with reduced efficacy. Given that no studies to date directly compare conservative measures with endovascular management for AIS in frail patients, more studies are required to further evaluate and identify characteristics that may improve outcomes in these patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Stroke is a prominent contributor to mortality and impairment on a global scale. Ischemic stroke accounts for approximately 80% of stroke cases and is caused by occlusion of cerebral blood vessels. Enhancing neurogenesis through the modulation of the neural stem cell niche in the adult brain is a promising therapeutic strategy for individuals afflicted with ischemic stroke. Neurogenesis results in the generation of newborn neurons that serve as replacements for deceased neural cells within the ischemic core, thereby playing a significant role in the process of neural restoration subsequent to cerebral ischemia. Research has shown that activation of the Wnt/β-catenin pathway can augment neurogenesis following cerebral ischemia, suggesting that this pathway is a potentially beneficial therapeutic target for managing ischemic stroke. This review provides an extensive analysis of the current knowledge regarding the involvement of the Wnt/β-catenin pathway in promoting neurogenesis, thereby offering a promising avenue for therapeutic intervention in the context of ischemic stroke or other neurological impairments., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Ischaemic stroke is a major cause of morbidity and mortality worldwide. Blood clotting and thromboembolism play a central role in the pathogenesis of ischaemic stroke. An increasing number of recent studies indicate changes in blood clot structure and composition in patients with ischaemic stroke. In this review, we aim to summarise and discuss clot structure, function and composition in ischaemic stroke, including its relationships with clinical diagnosis and treatment options such as thrombolysis and thrombectomy. Studies are summarised in which clot structure and composition is analysed both in vitro from patients' plasma samples and ex vivo in thrombi obtained through interventional catheter-mediated thrombectomy. Mechanisms that drive clot composition and architecture such as neutrophil extracellular traps and clot contraction are also discussed. We find that, while in vitro clot structure in plasma samples from ischaemic stroke patients are consistently altered, showing denser clots that are more resistant to fibrinolysis, current data on the composition and architecture of ex vivo clots obtained by thrombectomy are more variable. With the potential of advances in technologies underpinning both the imaging and retrieving of clots, we expect that future studies in this area will generate new data that is of interest for the diagnosis, optimal treatment strategies and clinical management of patients with ischaemic stroke., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Stroke is responsible for 11% of all deaths worldwide, the majority of which are caused by ischemic strokes, thus making the need to urgently find safe and effective therapies. Today, these can be cured either by mechanical thrombectomy when the thrombus is accessible, or by intravenous injection of fibrinolytics. However, the latter present several limitations, such as potential severe side effects, few eligible patients and low rate of partial and full recovery. To design safer and more effective treatments, nanomedicine appeared in this medical field a few decades ago. This review will explain why nanoparticle-based therapies and imaging techniques are relevant for ischemic stroke management. Then, it will present the different nanoparticle types that have been recently developed to treat this pathology. It will also study the various targeting strategies used to bring nanoparticles to the stroke site, thereby limiting side effects and improving the therapeutic efficacy. Finally, this review will present the few clinical studies testing nanomedicine on stroke and discuss potential causes for their scarcity., (Copyright © 2023 IBRO. Published by Elsevier Inc. All rights reserved.)

Ischemic stroke research has enabled significant advancements in diagnosis, treatment, and management of this debilitating disease, yet challenges remain standing in the way of better patient prognoses. In this narrative review, a fictional case illustrates challenges and uncertainties that medical professionals still face - penumbra identification, lack of neuroprotective agents, side-effects of tissue plasminogen activator, dearth of molecular biomarkers, incomplete microvascular reperfusion or no-reflow, post-recanalization hyperperfusion, blood pressure management and procedural anesthetic effects. The current state of the field is broadly reviewed per topic, with the aim to introduce a broad audience (scientist and clinician alike) to recent successes in translational stroke research and pending scientific queries that are tractable for preclinical assessment. Opportunities for co-operation between clinical and experimental stroke experts are highlighted to increase the size and frequency of strides the field makes to improve our understanding of this disease and ways of treating it., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Cerebral ischemia reperfusion injury (CIRI) often leads to deleterious complications after stroke patients receive reperfusion therapy. Exercise preconditioning (EP) has been reported to facilitate brain function recovery. We aim to explore the specific mechanism of EP in CIRI., Methods: Sprague-Dawley rats were randomized into Sham, middle cerebral artery occlusion (MCAO), and EP groups (n = 11). The rats in the EP group received adaptive training for 3 days (10 m/min, 20 min/day, with a 0° incline) and formal training for 3 weeks (6 days/week, 25 m/min, 30 min/day, with a 0° incline). Then, rats underwent MCAO surgery to establish CIRI models. After 48 h, neurological deficits and cerebral infarction of the rats were measured. Neuronal death and apoptosis in the cerebral cortices were detected. Furthermore, RNA sequencing was conducted to investigate the specific mechanism of EP on CIRI, and qPCR and Western blotting were further applied to confirm RNA sequencing results., Results: EP improved neurological deficit scores and reduced cerebral infarction in MCAO rats. Additionally, pre-ischemic exercise also alleviated neuronal death and apoptosis of the cerebral cortices in MCAO rats. Importantly, 17 differentially expressed genes (DEGs) were identified through RNA sequencing, and these DEGs were mainly enriched in the HIF-1 pathway, cellular senescence, proteoglycans in cancer, and so on. qPCR and Western blotting further confirmed that EP could suppress TIMP1, SOCS3, ANGPTL4, CDO1, and SERPINE1 expressions in MCAO rats., Conclusion: EP can improve CIRI in vivo, the mechanism may relate to TIMP1 expression and HIF-1 pathway, which provided novel targets for CIRI treatment., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

The precise and targeted delivery of therapeutic agents to the lesion sites remains a major challenge in treating brain diseases represented by ischemic stroke. Herein, we modified liposomes with mesenchymal stem cells (MSC) membrane to construct biomimetic liposomes, termed MSCsome. MSCsome (115.99 ± 4.03 nm) exhibited concentrated accumulation in the cerebral infarcted hemisphere of mice with cerebral ischemia-reperfusion injury, while showing uniform distribution in the two cerebral hemispheres of normal mice. Moreover, MSCsome exhibited high colocalization with damaged nerve cells in the infarcted hemisphere, highlighting its advantageous precise targeting capabilities over liposomes at both the tissue and cellular levels. Leveraging its superior targeting properties, MSCsome effectively delivered Dl-3-n-butylphthalide (NBP) to the injured hemisphere, making a single-dose (15 mg/kg) intravenous injection of NBP-encapsulated MSCsome facilitate the recovery of motor functions in model mice by improving the damaged microenvironment and suppressing neuroinflammation. This study underscores that the modification of the MSC membrane notably enhances the capacity of liposomes for precisely targeting the injured hemisphere, which is particularly crucial in treating cerebral ischemia-reperfusion injury., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Background: Early ischemic change and collateral extent are colinear with ischemic core volume (ICV). We investigated the relationship between a combined score using the Alberta Stroke Program Early Computed Tomography Score and multiphase computed tomography angiography (mCTA) collateral extent, named mCTA-ACE score, on functional outcomes in endovascular therapy-treated patients., Methods: We performed a post hoc analysis of a subset of endovascular therapy-treated patients from the Alteplase Compared to Tenecteplase trial which was conducted between December 2019 and January 2022 at 22 centers across Canada. Ten-point mCTA collateral corresponding to M2 to M6 regions of the Alberta Stroke Program Early Computed Tomography Score grid was evaluated as 0 (poor), 1 (moderate), or 2 (normal) and additively combined with the 10-point Alberta Stroke Program Early Computed Tomography Score to produce a 20-point mCTA-ACE score. We investigated the association of mCTA-ACE score with modified Rankin Scale score ≤2 and return to prestroke level of function at 90 to 120 days using mixed-effects logistic regression. In the subset of patients who underwent baseline computed tomography perfusion imaging, we compared the mCTA-ACE score and ICV for outcome prediction., Results: Among 1577 intention-to-treat population in the trial, 368 (23%; 179 men; median age, 73 years) were included, with Alberta Stroke Program Early Computed Tomography Score, mCTA collateral, and combination of both (mCTA-ACE score: median [interquartile range], 8 [7-10], 9 [8-10], and 17 [16-19], respectively). The probability of modified Rankin Scale score ≤2 and return to prestroke level of function increased for each 1-point increase in mCTA-ACE score (odds ratio, 1.16 [95% CI, 1.06-1.28] and 1.22 [95% CI, 1.06-1.40], respectively). Among 173 patients in whom computed tomography perfusion data was assessable, the mCTA-ACE score was inversely correlated with ICV (ρ=-0.46; P <0.01). The mCTA-ACE score was comparable to ICV to predict a modified Rankin Scale score ≤2 and return to prestroke level of function (C statistics 0.71 versus 0.69 and 0.68 versus 0.64, respectively)., Conclusions: The mCTA-ACE score had a significant positive association with functional outcomes after endovascular therapy and had a similar predictive performance as ICV., Competing Interests: Disclosures Dr Catanese reports compensation from Roche. Dr Shankar reports a grant from Medtronic. Dr Poppe reports grants from the Heart and Stroke Foundation of Canada, the Fondation Brain Canada, and Stryker and compensation from Roche. Dr Swartz reports grants from the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada; compensation from Roche and the Sunnybrook Research Institute; and stock holdings in FollowMD, Inc. Dr Hill reports grants from the Canadian Institutes of Health Research, Roche, Medtronic, MicroVention, Inc, Boehringer Ingelheim, and NoNO, Inc; compensation from Brainsgate and Merck; and a patent issued for Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients licensed to Circle Neurovascular Imaging. Dr Sajobi reports the role as a consultant to Circle Neurovascular Imaging. Dr Menon reports stock holdings in Circle Neurovascular Imaging and compensation from Roche and Boehringer Ingelheim. Dr Demchuk reports compensation from Roche, Lumosa, Boehringer Ingelheim, NovaSignal, Philips, and Medtronic; stock holdings in Circle Neurovascular Imaging; and a patent issued for Stroke imaging software licensed to Circle Neurovascular Imaging. Dr Ganesh reports grants from the Canadian Institutes of Health Research, the Alzheimer Society of Canada, the Heart and Stroke Foundation of Canada, the Fondation Brain Canada, the Sunnybrook Research Institute, the Canadian Cardiovascular Society, Alberta Innovates, Campus Alberta Neuroscience, the Government of Canada, Wellcome Trust, MicroVention, Inc, and Panmure House; compensation from the Canadian Association of Neuroscience Nurses, Biogen, and Atheneum for consultant services; MD Analytics, Creative Research Designs, CTC Communications, Corporation, Alexion Pharmaceuticals, Figure 1, Rhodes Scholarships, MyMedicalPanel, and DeepBench; and stock holdings in Collavidence, Inc, and SnapDx, Inc. Dr Ganesh is a Review Editor of Stroke for Frontiers in Neurology and an Editorial Board Member of Stroke of the American Heart Association and Neurology and Neurology: Clinical Practice of American Academy of Neurology and reports travel supports from the American Heart Association, the American Academy of Neurology, and the University of Calgary. The other authors report no conflicts.

Background: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well., Methods: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT., Results: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P <0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P =0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P =0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P =0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P =0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well., Conclusions: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248., Competing Interests: Disclosures Drs Demeestere and Lemmens reported institutional research fees from Genentech. Dr Strbian reported consultancy fees from AstraZeneca and Boehringer Ingelheim. Dr Nogueira reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda, Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, RapidPulse; stock options in Viz AI, Vesalio, Perfuze, Corindus, Brainomix, Ceretrieve; grants from Cerenovus and Stryker. Dr Nagel reported consultancy for Brainomix; speaker with Boehringer ingelheim and Pfizer. Dr Yamagami reported research grants from Bristol Myers Squibb; lecturer’s fees from Stryker, Medtronic, Johnson & Johnson, Bayer, Daiichi Sankyo, Bristol Myers Squibb, Otuska Pharmaceutical; advisory board for Daiichi Sankyo. Dr Puetz reported lecturer for Daiichi Sankyo. Dr Haussen reported consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; Data Safety and Monitoring Board from Jacobs Institute; and stock options in Viz AI. Dr Ribo reported consultancy for Medtronic, MiniMed, Cerenovus, AptaTargets, Stryker, Philips; stock holdings in Methinks, Nora, and Anaconda Biomed. Dr Michel reported grants from University of Lausanne and Swiss National Science Foundation (SNF). Dr Marto reported consulting from Amicus Therapeutics, Boehringer Ingelheim; Speaker with Boehringer Ingelheim. Dr Henon reported fees from Novartis and a grant from Sanofi-Aventis. Dr Gutierrez reported consultancy fees from Medtronic, Stryker and Microvention, and a grant from Methinks, Microvention, Stryker and the National Institutes of Health. Dr Siegler reported a grant from Philips and Viz AI. Dr Yoshimura reported research grants from Stryker, Siemens Healthineers, Bristol Myers Squibb, Sanofi, Eisai, Daiichi Sankyo, Teijin Pharma, Chugai Pharmaceutical, HEALIOS, Asahi Kasei Medical, Kowa, CSL Behring; lecturer fees from Stryker, Medtronic, Johnson & Johnson, Kaneka, Terumo, Biomedical Solutions, Boehringer Ingelheim, Daiichi Sankyo, Bayer and Bristol-Meyers Squibb. Dr Sheth reported consultancy for Imperative Care, Viz AI, Penumbra; compensation from Motif Neurosciences; grants from National Institutes of Health. Dr Dobrocky reported consultancy fees from MicroVention. Dr Kaesmacher reported grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. Dr Zaidi reported a grant from Genentech. Dr Castonguay reported employment by Medtronic. Dr Uchida reported fees by Bristol Myers Squibb, Daiichi Sankyo, Medtronic and Stryker. Dr Sakai reported research grant from Biomedical Solutions, Medtronic, Terumo, TG Medical; lecturer’s fees from Asahi-Intec, Biomedical Solutions, Daiichi Sankyo, Kaneka, Medtronic, Terumo; advisory board for Johnson & Johnson, Medtronic, Terumo. Dr Toyoda reported lecturer fees from Otsuka, Daiichi Sankyo, Bayer, Novartis, and Bristol-Myers Squibb. Dr Kaiser reported grants from the Joachim Herz Foundation. Dr Möhlenbruch reported grants from Medtronic, Stryker, and MicroVention. Dr Ringleb reported travel support from Bayer and Bristol Myers Squibb; consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. Dr Zaidat reported consultancy fees by Johnson & Johnson, Medtronic and Stryker, Penumbra stock, and a grant from Johson & Johnson, Medtronic, Penumbra and Stryker. Dr Fischer reported research support from SNF, Medtronic, Stryker, Rapid Medical, Penumbra, Phenox; consultancies for Stryker, CSL Behring; advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, Acthera. Dr Nguyen discloses research support from Medtronic to her institution; advisory board for Brainomix, Aruna Bio; Associate Editor Stroke.

Background: We aimed to examine the boundary of the ischemic core volume in patients undergoing endovascular thrombectomy (EVT) versus those receiving medical management to determine the minimum optimal size for favorable treatment outcomes., Methods: This is a prespecified substudy of the RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Large Ischemic Core Trial). Patients with large vessel occlusion were enrolled between November 2018 and September 2021 with a National Institutes of Health Stroke Scale score of at least 6 on admission and an Alberta Stroke Program Early Computed Tomography Score value of 3 to 5. We investigated the correlation between optimal quantified ischemic core volume, assessed solely using magnetic resonance diffusion-weighted imaging, and functional outcomes (modified Rankin Scale score, 0-3) at 90 days by predictive marginal plots. Final infarct volume and safety outcomes (symptomatic intracerebral hemorrhage and mortality) were also assessed., Results: Of the 203 cases, 168 patients (85 in the EVT group versus 83 in the medical management group) were included. The median (interquartile range) core volume was 94 (65-160) mL in patients with EVT and 115 (71-141) mL in the medical management group ( P =0.72). The predictive marginal probabilities of the 2 groups intersected at 128 mL for estimating functional outcomes. Symptomatic intracerebral hemorrhage and mortality within 90 days had overlay margins through all core volumes in both groups. The median final infarct volume (interquartile range) was smaller in the EVT group (142 [80-223] mL versus 211 [123-289] mL in the medical management group; P <0.001)., Conclusions: In this prespecified analysis of a randomized clinical trial involving patients with large ischemic strokes, patients with an estimated core volume of up to 128 mL on diffusion-weighted imaging benefit from EVT., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03702413., Competing Interests: Disclosures Dr Inoue reports the lecturer’s fees from Bayer, Bristol-Myers Squibb, and Nippon Boehringer Ingelheim. Dr Yoshimoto reports lecture fees from Takeda Pharmaceutical and Nippon Boehringer Ingelheim. Dr Toyoda reports lecture fees from Bayer, Daiichi Sankyo, Takeda, and Bristol-Myers Squibb. Dr Yamagami discloses research grants from Bristol-Myers Squibb; lecturer’s fees from Stryker, Medtronic, Terumo, Johnson & Johnson, Biomedical Solutions, and Medico’s Hirata; and membership of the advisory boards for Daiichi Sankyo. Dr Sakai reports research grants from Biomedical Solutions, Daiichi Sankyo, and Terumo; lecturer’s fees from Asahi-Intec, Biomedical Solutions, Daiichi Sankyo, and Medtronic; and membership on the advisory boards for Johnson & Johnson, Medtronic, and Terumo. Dr Matsumaru reports lecturer fees from Medtronic, Stryker, Terumo, Johnson & Johnson, Kaneka, and Jimro. Dr Matsumoto reports the lecturer’s fees from Kaneka, Medico’s Hirata, Fuji systems, GE Healthcare, Otsuka, Takeda, Century Medical, Terumo, Medtronic, and Stryker. Dr Kimura reports research grants from CSL Behring, Eisai, Kyowa Kirin, Daiichi Sankyo, Teijin, Medtronic, Bristol-Myers Squibb, Bayer, Boehringer Ingelheim, Helios; and lecturer’s fees from Daiichi Sankyo, Boehringer Ingelheim, Bristol-Myers Squibb, Bayer, Takeda, Medtronic, Otsuka, FP, Alexion, Sanofi, CSL Behring, Novartis, Toa Eiyo, Medico’s Hirata, and Helios. Dr Uchida reports lecturer’s fees from Daiichi Sankyo, Bristol-Myers Squibb, Stryker, and Medtronic. Dr Beppu reports manuscript fees from Medicus Shuppan. Dr Sakakibara reports manuscript fees from Medicus Shuppan. Dr Morimoto reports lecturer’s fees from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Pfizer, and Tsumura; manuscript fees from Bristol-Myers Squibb and Pfizer; advisory board for Novartis and Teijin. Dr Yoshimura reports research grants from Medico’s Hirata, Medtronic, and Terumo; and lecturer fees from Medtronic, Kaneka, Stryker, Daiichi Sankyo, Bristol-Meyers Squibb, and Johnson & Johnson. The other author reports no conflicts.

Nanozymes are a new kind of material which has been applied since the beginning of this century, and its birth has promoted the development of chemistry, materials science, and biology. Nanozymes can be used as a substitute for natural enzyme and has a wide range of applications; therefore, it has attracted extensive attention from all sectors of the community, and the number of studies has constantly increasing. In this paper, we introduced the outstanding achievements in the field of nanozymes in recent years from the main function, the construction of nanozyme-based biosensors, and the treatment of ischemic stroke, and we also illustrated the internal mechanism and the catalytic principle. In the end, the obstacles and challenges in the future development of nanozymes were proposed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Stroke represents one of the neurological diseases most responsible for death and permanent disability in the world. Different factors, such as thrombus, emboli and atherosclerosis, take part in the intricate pathophysiology of stroke. Comprehending the molecular processes involved in this mechanism is crucial to developing new, specific and efficient treatments. Some common mechanisms are excitotoxicity and calcium overload, oxidative stress and neuroinflammation. Furthermore, non-coding RNAs (ncRNAs) are critical in pathophysiology and recovery after cerebral ischemia. ncRNAs, particularly microRNAs, and long non-coding RNAs (lncRNAs) are essential for angiogenesis and neuroprotection, and they have been suggested to be therapeutic, diagnostic and prognostic tools in cerebrovascular diseases, including stroke. This review summarizes the intricate molecular mechanisms underlying ischemic and hemorrhagic stroke and delves into the function of miRNAs in the development of brain damage. Furthermore, we will analyze new perspectives on treatment based on molecular mechanisms in addition to traditional stroke therapies.

Poststroke cognitive impairment (PSCI) is a common complication of stroke, but effective treatments are currently lacking. Repetitive transcranial magnetic stimulation (rTMS) is gradually being applied to treat PSCI, but there is limited evidence of its efficacy. To determine rTMS effects on PSCI, we constructed a transient middle cerebral artery occlusion (tMCAO) rat model. Rats were then grouped by random digital table method: the sham group (n = 10), tMCAO group (n = 10) and rTMS group (n = 10). The shuttle box and Morris water maze (MWM) tests were conducted to detect the cognitive functions of the rats. In addition, synaptic density and synaptic ultrastructural parameters, including the active zone length, synaptic cleft width, and postsynaptic density (PSD) thickness, were quantified and analyzed using an electron microscope. What's more, synaptic associated proteins, including PSD95, SYN, and BDNF were detected by western blot. According to the shuttle box and MWM tests, rTMS improved tMCAO rats' cognitive functions, including spatial learning and memory and decision-making abilities. Electron microscopy revealed that rTMS significantly increased the synaptic density, synaptic active zone length and PSD thickness and decreased the synaptic cleft width. The western blot results showed that the expression of PSD95, SYN, and BDNF was markedly increased after rTMS stimulation. Based on these results, we propose that 20 Hz rTMS can significantly alleviate cognitive impairment after stroke. The underlying mechanism might be modulating the synaptic plasticity and up-regulating the expression PSD95, SYN, and BDNF in the hippocampus., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To observe the angiogenesis effect of electroacupuncture (EA) at Shuigou acupoint (GV 26) in the treatment of cerebral ischemia, and explore the value of miRNA-7 (miR-7) in it., Methods: First, 48 mice were randomly divided into sham operation, middle cerebral artery occlusion (MCAO) model, and EA treatment groups. Then 9 mice were divided into carrier control group, miR-7 knockout group and miR-7 overexpression group (n=3 each group). Finally, 20 mice were divided into model and carrier control group, model and miR-7 knockout group, EA treatment and carrier control group and EA treatment and miR-7 overexpression group, with 3-6 mice in each group. The MCAO model was established in the MCAO and EA groups. Neurological deficit score and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to evaluate the severity of cerebral ischemia. Hematoxylin-eosin staining was used to describe basic pathological changes. Immunohistochemistry was used to quantify cerebral microvessel density. Real-time PCR and Western blot were used to detect the expression of miR-7 and its downstream target genes Krüppel-like factor 4/vascular endothelial growth factor (KLF4/VEGF) and angiopoietin-2 (ANG-2) in the ischemic cerebral cortex., Results: After EA, neurological deficit scores and infarction volumes decreased, and the density of cerebral microvessels increased. In the MCAO group, miR-7 expression was higher than that in the sham group (P<0.01). After EA at GV 26, miR-7 expression decreased (P<0.01) and the expression of downstream target genes KLF4/VEGF and ANG-2 increased as compared with the MCAO group (P<0.01). After EA combined with overexpression of miR-7, the expression of downstream target genes KLF4/VEGF and ANG-2 decreased compared to the control EA group (P<0.01). After miR-7 knockdown, the expression of KLF4/VEGF and ANG-2 increased (P<0.05 or P<0.01)., Conclusions: EA could promote angiogenesis in MCAO mice likely by inhibiting the expression of miR-7 and relieving inhibition of downstream target genes KLF4/VEGF and ANG-2., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Present-day computer tomography (CT) scanners have excellent spatial resolution and signal-to-noise ratio and are instrumental detecting early ischemic changes (EIC) in brain. We assessed the temporal changes of EIC based on the recanalization status after thrombectomy., Patients and Methods: The cohort comprises consecutive patients with acute ischemic stroke in anterior circulation treated with thrombectomy in tertiary referral hospital. All baseline and follow-up scans were screened for any ischemic changes and further classified using Alberta Stroke Program Early CT Score (ASPECTS). Generalized linear mixed models were used to analyze the impact of recanalization status using modified Thrombolysis in Cerebral Infarction (mTICI) on temporal evolution of ischemic changes., Results: We included 614 patients with ICA, M1, or M2 occlusions. Median ASPECTS score was 9 (IQR 7-10) at baseline and 7 (5-8) at approximately 24 h. mTICI 3 was achieved in 207 (33.8%), 2B 241 (39.3%), 2A in 77 (12.6%), and 0-1 in 88 (14.3%) patients. Compared to patients with mTICI 3, those with mTICI 0-1 and 2A had less favorable temporal changes of ASPECTS ( p  < 0.001). Effect of recanalization was noted in the cortical regions of ICA/M1 patients, but not in their deep structures or patients with M2 occlusions. All ischemic changes detected at baseline were also present at all follow-up images, regardless of the recanalization status., Conclusions: Temporal evolution of the ischemic changes and ASPECTS are related to the success of the recanalization therapy in cortical regions of ICA/M1 patients, but not in their deep brain structures or M2 patients. In none of the patients did EIC revert in any brain region after successful recanalization., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The failure of neuroprotective treatment-related clinical trials, including stem cell therapies, may be partially due to a lack of suitable animal models. We have developed a stem cell-implantable radiopaque hydrogel microfiber that can survive for a long time in vivo. The microfiber is made of barium alginate hydrogel containing zirconium dioxide, fabricated in a dual coaxial laminar flow microfluidic device. We aimed to develop a novel focal stroke model using this microfiber. Using male Sprague-Dawley rats (n=14), a catheter (inner diameter, 0.42 mm; outer diameter, 0.55 mm) was navigated from the caudal ventral artery to the left internal carotid artery using digital subtraction angiography. A radiopaque hydrogel microfiber (diameter, 0.4 mm; length, 1 mm) was advanced through the catheter by slow injection of heparinized physiological saline to establish local occlusion. Both 9.4-T magnetic resonance imaging at 3 and 6 h and 2% 2,3,5-triphenyl tetrazolium chloride staining at 24 h after stroke model creation were performed. Neurological deficit score and body temperature were measured. The anterior cerebral artery-middle cerebral artery bifurcation was selectively embolized in all rats. Median operating time was 4 min (interquartile range [IQR], 3-8 min). Mean infarct volume was 388 mm 3 (IQR, 354-420 mm 3 ) at 24 h after occlusion. No infarction of the thalamus or hypothalamus was seen. Body temperature did not change significantly over time (P = 0.204). However, neurological deficit scores before and at 3, 6, and 24 h after model creation differed significantly (P < 0.001). We present a novel rat model of focal infarct restricted to the middle cerebral artery territory using a radiopaque hydrogel microfiber positioned under fluoroscopic guidance. By comparing the use of stem cell-containing versus non-containing fibers in this stroke model, it would be possible to determine the efficacy of "pure" cell transplantation in treating stroke., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Global ischemic brain injury is the leading cause of mortality and long-term disability in patients resuscitated from cardiac arrest. Hypothermia and neuroprotective agents are two strategies partially improve neurological outcomes following resuscitation. However, the therapeutic effects of these treatments are inconsistently reported. Stem cell therapy has emerged as a promising protective strategy due to its potential for proliferation and differentiation into functional neural cells. This editorial reviews the current status of stem cell therapy via the intranasal route in primates and clinical studies, along with the treatment window of stem cell therapy in ischemic brain injury after cardiac arrest to provide new insight into stem cell therapy for cardiac arrest-induced global cerebral ischemia injury., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Numerous evidences showed that human umbilical cord blood (UCB) mononuclear cells were a promising approach for the therapy of ischemic stroke(IS). The effect of stage-specific embryonic antigen 3 (SSEA3）positive subpopulation in UCB was not investigated in IS. In this study, we isolated SSEA3 positive cells from healthy UCB mononuclear cells, which comprised about 7.01% of the total UCB-mononuclear cells. Flow cytometry analysis revealed that SSEA3(+)UCB cells were almost positive for CD44 and CD45, and negative for CD73, CD90 and CD105. The expression of Oct3/4 in SSEA3(+)UCB cells were higher than that in UCB. SSEA3(+)UCB cells sorted by magnetic cell sorting were intravenously injected into the middle cerebral arterial occlusion(MCAO) rat model. Neurological score showed that SSEA3(+)UCB transplantation group exhibited significant improvements in the functional outcome of MCAO rats than UCB transplantation group. Nissl staining and microtubule association protein-2(MAP2) immunofluorescence staining showed that the SSEA3(+)UCB transplantation group decreased neuronal loss. SSEA3(+)UCB transplantation group reduced neuronal apoptosis, inhibited caspase3 expression, and decreased tumor necrosis factor α(TNF-α). These results indicate that SSEA3 positive cells are a novel subpopulation of UCB cells, which exhibit great potential for the treatment of ischemic stroke., Competing Interests: Decalartion of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Oxidative stress and inflammatory responses play essential roles in cerebral ischemia/reperfusion (I/R) injury. Electroacupuncture (EA) is widely used as a rehabilitation method for stroke in China; however, the underlying mechanism of action remains unclear. Peroxisome proliferator-activated receptor gamma (PPAR-γ) has been reported to impact anti-inflammatory and anti-oxidative effects., Objective: This study investigated the role of PPAR-γ in EA-mediated effects and aimed to illuminate its possible mechanisms in cerebral I/R., Methods: In this study, male Sprague-Dawley (SD) rats with middle cerebral artery occlusion/reperfusion (MCAO/R) injury were treated with EA at LI11 and ST36 for 30 min daily after MCAO/R for seven consecutive days. The neuroprotective effects of EA were measured by neurobehavioral evaluation, triphenyltetrazolium chloride staining, hematoxylin-eosin staining and transmission electron microscopy. Oxidative stress, inflammatory factors, neural apoptosis and microglial activation were examined by enzyme-linked immunosorbent assay, immunofluorescence and reverse transcriptase polymerase chain reaction. Western blotting was used to assess PPAR-γ-mediated signaling., Results: We found that EA significantly alleviated cerebral I/R-induced infarct volume, decreased neurological scores and inhibited I/R-induced oxidative stress, inflammatory responses and microglial activation. EA also increased PPAR-γ protein expression. Furthermore, the protective effects of EA were reversed by injection of the PPAR-γ antagonist T0070907., Conclusion: EA attenuates cerebral I/R injury by regulating oxidative stress, neuronal death and neuroinflammation via stimulation of PPAR-γ., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

To study the protective mechanism of acupuncture at "Jiangya Recipe" on chronic ischemic white matter injury in spontaneously hypertensive rats (SHR) and the regulation of Jun N-terminal kinase-N-methyl-D-aspartate receptor (JNK-NMDAR) loop. A hypertensive white matter injury model was established in 46 male SHR rats aged 11 weeks by bilateral common carotid artery tapering (SHR-2VGO). In the SHR sham operation group, only bilateral common carotid arteries were isolated and in the SHR-2VGO modeling group, 36 rats were used for microcoil spring clip implantation to narrow the common carotid arteries and then, after 2 weeks of modeling, rats with impaired motor function were removed, and SHR-2VGO rats with successful final models were randomly divided into the model group, JNK blocking group, and acupuncture group. The sham operation group, model group, and JNK blocking group underwent the same grasping fixation, and the acupuncture group received acupuncture at acupoints "Jiangya Fang" once daily. In the JNK blocker group, an injection cannula was implanted into the lateral ventricle and sp600125 was injected into the lateral ventricle at 4.5 ul/day for 4 weeks. One week after the end of the intervention, white matter lesions were detected by MRI DWI and T2 imaging, and the learning and memory ability of rats was tested by Y-Maze and Passive Avoidance. Myelin density was detected by luxol fast blue (LFB) staining, also axon arrangement, myelin integrity, and thickness of neurons were detected by electron microscopy; neuronal morphology and the number of Nissl bodies in the hippocampus were detected by Nissl staining, dendritic spine density changes were detected by Golgi staining, and JNK, NMDAR1, and N-methyl-D-receptor 2B (NMDAR2B) in DG, CA3 region of hippocampus were detected by immunohistochemistry, protein expression of p-JNK/JNK, p-NMDAR1/NMDAR1, NMDAR2B, GSK3β protein expression in the fimbria of hippocampus was detected by Western blot. The Y maze test of SHR-2VGO+Acu and SHR-2VGO+ sp600125 group showed that the spontaneous alternating reaction rate increased significantly. At the same time, the incubation period increased significantly and the number of errors decreased significantly in Passive Avoidance. MRI T2WI showed that the white matter high signal of the corpus callosum, internal capsule and hippocampal fimbria in the SHR-2VGO+ sp600125 and SHR-2VGO+Acu groups was significantly lower than that in the SHR-2VGO model group, and the striatum and anterior commissure were not obvious. DWI showed that the SHR-2VGO model group had scattered high signal and limited diffusion movement in both the internal capsule and striatum, but the difference between groups was not obvious. Compared with SHR-2VGO rats, LFB staining of SHR-2VGO + sp600125 and SHR-2VGO +Acu groups showed significant relaxation of myelin porosity in corpus callosum, striatum, inner capsule, anterior commissure and hippocampal fimbria, and electron microscopy showed improved axonal myelin integrity and thickness in corpus callosum region. Also, the number of blue patchy Nissl bodies increased, and the number and complexity of dendritic spines increased significantly in Golgi staining. Immunohistochemical detection showed that JNK levels in DG and CA3 region were increased and NMDAR1 and NMDAR2B levels were decreased in SHR-2VGO+Acu and SHR-2VGO+ sp600125 groups. Meanwhile, protein expressions of GSK3β, NMDAR1/p-NMDAR1 and NMDAR2B in fimbria of hippocampus were increased, and JNK/P-JNK protein expression decreased. Acupuncture can increase the density and thickness of myelin sheath in white matter areas of corpus callosum, anterior commissure and hippocampal fimbria, increase the number and length of hippocampal neuronal dendrites, and improve hypertensive white matter injury and cognitive decline through JNK-NMDAR pathway., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The treatment for cerebral ischemia remains limited, and new therapeutic strategies are urgently needed. Exosome has shown great promise for the treatment of cerebral ischemia. Steroid receptor coactivator-3 (SRC-3) was reported to be involved in neurological performances. In this study, we aimed to investigate the protective effects of mesenchymal stem cell (MSC)-derived exosomes overexpressing SRC-3 on cerebral ischemia in mice., Methods: The mice were treated with an intracerebroventricular injection of GFP-overexpressed exosomes (GFP-exo) and SRC-3-overexpressed exosomes (SRC3-exo) in a middle cerebral artery occlusion (MCAO) model of cerebral ischemia., Results: The results showed that SRC3-exo treatment significantly inhibited lipid peroxidation and ferroptosis of the neurons subjected to oxygen-glucose deprivation. It further suppressed the activation of microglia and astrocytes, and decreased the production of pro-inflammatory cytokines in the brains of MCAO mice. Furthermore, SRC3-exo treatment reduced the water content of brain tissue and infarct size, which alleviated the neurological damage and improved neurological performances in the MCAO mice., Conclusions: Our results suggest that MSC-derived exosomes expressing SRC3 can be a therapeutic strategy for cerebral ischemia by inhibiting ferroptosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Stroke is a devastating disease affecting populations worldwide and is the primary cause of long-term disability. The inflammatory storm plays a crucial role in the progression of stroke. In the acute phase of ischemic stroke, there is a transient increase in anti-inflammatory M2 microglia followed by a rapid decline. Due to the abundant phospholipid in brain tissue, lipid peroxidation is a notable characteristic of ischemia/reperfusion (I/R), constituting a structural foundation for ferroptosis in M2 microglia. Slowing down the decrease in M2 microglia numbers and controlling the inflammatory microenvironment holds significant potential for enhancing stroke recovery., Results: We found that the ferroptosis inhibitor can modulate inflammatory response in MCAO mice, characterizing that the level of M2 microglia-related cytokines was increased. We then confirmed that different subtypes of microglia exhibit distinct sensitivities to I/R-induced ferroptosis. Adipose-derived stem cells derived exosome (ADSC-Exo) effectively decreased the susceptibility of M2 microglia to ferroptosis via Fxr2/Atf3/Slc7a11, suppressing the inflammatory microenvironment and promoting neuronal survival. Furthermore, through plasmid engineering, a more efficient M2 microglia-targeted exosome, termed M2pep-ADSC-Exo, was developed. In vivo and in vitro experiments demonstrated that M2pep-ADSC-Exo exhibits significant targeting specificity for M2 microglia, further inhibiting M2 microglia ferroptosis and improving neurological function in ischemic stroke mice., Conclusion: Collectively, we illustrated a novel potential therapeutic mechanism that Fxr2 in ADSC-Exo could alleviate the M2 microglia ferroptosis via regulating Atf3/Slc7all expression, hence inhibiting the inflammatory microenvironment, improving neurofunction recovery in cerebral I/R injury. We obtained a novel exosome, M2pep-ADSC-Exo, through engineered modification, which exhibits improved targeting capabilities toward M2 microglia. This provides a new avenue for the treatment of stroke., (© 2024. The Author(s).)

Objectives: To observe the effect of electro-scalp acupuncture (ESA) on the expression of cytochrome P450a1/b1 (CYP27a1/b1), cytochrome P45024a (CYP24a), signal transducer and activator of transcription (STAT)4, STAT6, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-4 in ischemic cerebral cortex of rats with acute ischemic stroke, so as to explore its mechanism in alleviating inflammatory reaction of ischemic stroke., Methods: Sixty SD rats were randomly divided into sham-operation, model, vitamin D 3 and ESA groups, with 15 rats in each group. The middle cerebral artery occlusion rat model was established with thread ligation according to Zea-Longa's method. Rats in the vitamin D 3 group were given 1, 25-VitD 3 solution (3 ng·100 g -1 ·d -1 ) by gavage, once daily for 7 days. Rats in the ESA group were treated at bilateral anterior parietotemporal slash (MS6) with ESA (2 Hz/100 Hz, 1 mA), 30 min a day for 7 days. Before and after interventions, the neurological deficit score and neurobehavioral score were evaluated. TTC staining was used to detect the volume of cerebral infarction in rats. The positive expressions of CYP24a, CYP27a1 and CYP27b1 in the cerebral cortex of ischemic area were detected by immunofluorescence. The mRNA expressions of STAT4 and STAT6 in the cerebral cortex of ischemic area were detected by quantitative real-time PCR. The protein expression levels of TNF-α, IL-1β and IL-4 in the cerebral cortex of ischemic area were detected by Western blot., Results: Compared with the sham-operation group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1β in cerebral cortex were increased ( P <0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA, protein expression level of IL-4 were decreased ( P <0.01) in the model group. After the treatment and compared with the model group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1β in cerebral cortex were decreased ( P <0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA expression level, protein expression level of IL-4 were increased ( P <0.01) in the ESA and vitamin D 3 groups., Conclusions: ESA can alleviate the inflammatory response in ischemic stroke, which maybe related to its function in regulating the balance between CYP27a1/b1 and CYP24a, converting vitamin D into active vitamin D 3 , inhibiting vitamin D 3 degradation, and regulating Th1/Th2 balance.

Acute ischemic stroke (AIS) is a challenging disease, which needs urgent comprehensive management. Endovascular thrombectomy (EVT), alone or combined with iv thrombolysis, is currently the most effective therapy for patients with acute ischemic stroke (AIS). However, only a limited number of patients are eligible for this time-sensitive treatment. Even though there is still significant room for improvement in the management of this group of patients, up until now there have been no alternative therapies approved for use in clinical practice. However, there is still hope, as clinical research with novel emerging therapies is now generating promising results. These drugs happen to stop or palliate some of the underlying molecular mechanisms involved in cerebral ischemia and secondary brain damage. The aim of this review is to provide a deep understanding of these mechanisms and the pathogenesis of AIS. Later, we will discuss the potential therapies that have already demonstrated, in preclinical or clinical studies, to improve the outcomes of patients with AIS.

Mast cells (MCs) play a significant role in various diseases, and their activation and degranulation can trigger inflammatory responses and barrier damage. Several studies have indicated that vagus nerve stimulation (VNS) exerts ameliorates neurological injury, and regulates gut MC degranulation. However, there is limited research on the modulatory effect of VNS on MCs in both the gut and brain in brain ischemia-reperfusion (I/R) injury in this process. We aim to develop a minimally invasive, targeted and convenient VNS approach to assess the impact of VNS and to clarify the relationship between VNS and MCs on the prognosis of acute ischemic stroke. We utilized middle cerebral artery occlusion/reperfusion (MCAO/r) to induce brain I/R injury. After the experiment, the motor function and neurofunctional impairments of the rats were detected, and the gastrointestinal function, blood-brain barrier (BBB) and intestinal barrier damage, and systemic and local inflammation were evaluated by Nissl, TTC staining, Evans blue, immunofluorescence staining, transmission electron microscopy, western blot assays, ELISA, and fecal 16S rRNA sequencing methods. Our research confirmed that our minimally invasive VNS method is a novel approach for stimulating the vagus nerve. VNS alleviated motor deficits and gastrointestinal dysfunction while also suppressing intestinal and neuroinflammation. Additionally, VNS ameliorated gut microbiota dysbiosis in rats. Furthermore, our analysis indicated that VNS reduces chymase secretion by modulating MCs degranulation and improves intestinal and BBB damage. Our results showed that VNS treatment can alleviate the damage of BBB and colonic barrier after cerebral I/R by modulating mast cell degranulation, and alleviates systemic inflammatory responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Biological sex is known to have an impact on quality metrics of acute stroke. We aimed to determine whether COVID positivity accentuates this effect and constitutes worse outcome., Methods: The present analysis was based on the Global COVID-19 Stroke Registry, a retrospective, international, cohort study of consecutive ischemic stroke patients receiving intravenous thrombolysis and/or endovascular thrombectomy between 1 March 2020 and 30 June 2021. We investigated differences between the sexes in patient characteristics, acute stroke metrics as well as post-stroke outcome in COVID-positive and COVID-negative stroke patients undergoing acute revascularization procedures., Results: A total of 15,128 patients from 106 centers were recorded in the Global COVID-19 Stroke Registry, 853 (5.6%) of whom were COVID-positive. Overall, COVID-positive individuals were treated significantly slower according to every acute stroke metric compared to COVID-negative patients. We were able to show that key quality indicators in acute stroke treatment were unfavorable for COVID-negative women compared to men (last-seen-well-to-door time + 11 min in women). Furthermore, COVID-negative women had worse 3-month outcomes (3-month modified Rankin Scale score [interquartile range] 3.0 [4.0] vs. 2.0 [3.0]; p < 0.01), even after adjusting for confounders. In COVID-positive individuals no such difference between the sexes, either in acute management metrics or in 3-month outcome, was seen., Conclusion: Known sex-related differences in acute stroke management exist and extend to times of crisis. Nevertheless, if patients were COVID-19-positive at stroke onset, women and men were treated the same, which could be attributed to structured treatment pathways., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Electroacupuncture (EA) has been shown to facilitate brain plasticity-related functional recovery following ischemic stroke. The functional magnetic resonance imaging technique can be used to determine the range and mode of brain activation. After stroke, EA has been shown to alter brain connectivity, whereas EA's effect on brain network topology properties remains unclear. An evaluation of EA's effects on global and nodal topological properties in rats with ischemia reperfusion was conducted in this study., Methods and Results: There were three groups of adult male Sprague-Dawley rats: sham-operated group (sham group), middle cerebral artery occlusion/reperfusion (MCAO/R) group, and MCAO/R plus EA (MCAO/R + EA) group. The differences in global and nodal topological properties, including shortest path length, global efficiency, local efficiency, small-worldness index, betweenness centrality (BC), and degree centrality (DC) were estimated. Graphical network analyses revealed that, as compared with the sham group, the MCAO/R group demonstrated a decrease in BC value in the right ventral hippocampus and increased BC in the right substantia nigra, accompanied by increased DC in the left nucleus accumbens shell (AcbSh). The BC was increased in the right hippocampus ventral and decreased in the right substantia nigra after EA intervention, and MCAO/R + EA resulted in a decreased DC in left AcbSh compared to MCAO/R., Conclusion: The results of this study provide a potential basis for EA to promote cognitive and motor function recovery after ischemic stroke., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objectives: The aim was to investigate whether the angiographic demonstration of a cutoff sign on the initial angiogram could predict recanalization and prognosis in acute ischemic stroke patients treated by endovascular thrombectomy., Methods: The angiographic and clinical data of patients who underwent endovascular treatment from October 2018 to April 2023 were retrospectively reviewed. The pretreatment angiographic appearance of the thrombus's proximal part was assessed and classified as either the cutoff sign (+) or (-). Patients' baseline characteristics and angiographic and clinical outcomes between the two groups were analyzed using propensity score matching. Then, the two commonly used techniques, stent retrieval and contact aspiration, were compared in terms of successful reperfusion and clinical outcome in patients with the cutoff sign., Results: The cutoff sign was observed in 77 (36.2%) of 213 patients. Patients with the cutoff sign were younger and were less likely to have involvement of the anterior circulation. Compared with the cutoff sign (-) group, the cutoff sign (+) group had a significantly longer procedure time (103 versus 80 min, P =0.002) and a lower percentage of 3-month good functional outcomes (18.2% versus 36%, P =0.006). After propensity score matching, the procedure time (100 versus 75 min, P =0.002) and the 3-month good outcome (19.2% versus 41.4%, P =0.004) remained significantly different. No significant differences were observed in the radiological (OR 0.758, 95% CI 0.157 to 3.658; P =0.730) and clinical (OR 0.747, 95% CI 0.147 to 3.787; P =0.725) outcomes between the two techniques., Conclusions: The cutoff sign might be an unfavorable prognostic indicator in patients undergoing mechanical thrombectomy, and the efficacy of mechanical thrombectomy techniques does not differ in patients positive for the cutoff sign., Competing Interests: Declaration of competing interest All authors declared no potential conflicts of interest with respect to the research, author-ship, and publication of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: CT perfusion of the brain is a powerful tool in stroke imaging, though the radiation dose is rather high. Several strategies for dose reduction have been proposed, including increasing the intervals between the dynamic scans. We determined the impact of temporal resolution on perfusion metrics, therapy decision, and radiation dose reduction in brain CT perfusion from a large dataset of patients with suspected stroke., Methods: We retrospectively included 3555 perfusion scans from our clinical routine dataset. All cases were processed using the perfusion software VEOcore with a standard sampling of 1.5 s, as well as simulated reduced temporal resolution of 3.0, 4.5, and 6.0 s by leaving out respective time points. The resulting perfusion maps and calculated volumes of infarct core and mismatch were compared quantitatively. Finally, hypothetical decisions for mechanical thrombectomy following the DEFUSE-3 criteria were compared., Results: The agreement between calculated volumes for core (ICC = 0.99, 0.99, and 0.98) and hypoperfusion (ICC = 0.99, 0.99, and 0.97) was excellent for all temporal sampling schemes. Of the 1226 cases with vascular occlusion, 14 (1%) for 3.0 s sampling, 23 (2%) for 4.5 s sampling, and 63 (5%) for 6.0 s sampling would have been treated differently if the DEFUSE-3 criteria had been applied. Reduction of temporal resolution to 3.0 s, 4.5 s, and 6.0 s reduced the radiation dose by a factor of 2, 3, or 4., Conclusion: Reducing the temporal sampling of brain perfusion CT has only a minor impact on image quality and treatment decision, but significantly reduces the radiation dose to that of standard non-contrast CT., (© 2024. The Author(s).)

Background: While endovascular thrombectomy (EVT) is beneficial for patients with acute large vessel occlusion ischemic strokes, a significant portion of patients still do poorly despite successful recanalization. Identifying patients at high risk for poor outcomes can be helpful for future clinical trial design and optimizing acute stroke triage., Methods: Consecutive EVT patients were identified from 2016 to 2021 at a Comprehensive Stroke Center, and clinical information was recorded. Poor outcome was defined as a 90-day modified Rankin Scale (mRS) of 4 or greater despite achieving a modified thrombolysis in cerebral infarction (mTICI) score of 2b or greater. Multivariable regression analyses were used to identify risk factors for poor outcomes, and a scoring system was constructed., Results: 483 patients with successful recanalization were identified. From a randomly selected training cohort (n = 357), the 10-point BAND score was constructed from independent risk factors for poor outcomes: baseline disability (1 point: baseline mRS ≥ 2), age (1 point: 60-69 years, 2 points: 70-79 years, 3 points: 80-84 years, 4 points: 85 years or older), NIHSS (2 points: 13-17, 3 points: 18-22, and 4 points: ≥ 23), and delay from last known normal (1 point: ≥ 6 h). The BAND score was significantly associated with rates of poor outcomes (p < 0.001), and it achieved an area under the receiver-operating characteristic curve (AUC) of 0.80 (95 %CI 0.76-0.85) in our training cohort and 0.78 (95 %CI 0.70-0.86) in our validation cohort (n = 126). Overall, the BAND score had a significantly higher AUC value than the widely validated THRIVE score and the THRIVE-EVT calculation (p = 0.001 and 0.029, respectively). Among patients with high BAND scores (7 or higher), 88.2 % had poor outcomes., Conclusion: The BAND score is a simple tool to predict poor outcomes despite successful recanalization. Future studies are needed to confirm the BAND score's external validity., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aimed to investigate the intervention effect of tetramethylpyrazine(TMP) combined with transplantation of neural stem cells(NSCs) on middle cerebral artery occlusion(MCAO) rat model and to explore the mechanism of TMP combined with NSCs transplantation on ischemic stroke based on the regulation of stem cell biological behavior. MCAO rats were randomly divided into a model group, a TMP group, an NSCs transplantation group, and a TMP combined with NSCs transplantation group according to neurological function scores. A sham group was set up at the same time. The neurological function score was used to evaluate the improvement of neurological function in MCAO rats after TMP combined with NSCs transplantation. The proliferation, migration, and differentiation of NSCs were evaluated by BrdU, BrdU/DCX, BrdU/NeuN, and BrdU/GFAP immunofluorescence labeling. The protein expression of stromal cell-derived factor 1(SDF-1), C-X-C motif chemokine receptor 4(CXCR4), as well as oxidative stress pathway proteins nuclear factor erythroid 2-related factor 2(Nrf2), Kelch-like ECH-associated protein 1(KEAP1), heme oxygenase 1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1) was detected by Western blot to study the migration mechanism of TMP combined with NSCs. The results showed that TMP combined with NSCs transplantation significantly improved the neurological function score in MCAO rats. Immunofluorescence staining showed a significant increase in the number of BrdU~+, BrdU~+/DCX~+, BrdU~+/NeuN~+, and BrdU~+/GFAP~+ cells in the TMP, NSCs transplantation, and combined treatment groups, with the combined treatment group showing the most significant increase. Further Western blot analysis revealed significantly elevated expression of CXCR4 protein in the TMP, NSCs transplantation, and combined treatment groups, along with up-regulated protein expression of Nrf2, HO-1, and NQO1, and decreased KEAP1 protein expression. This study showed that both TMP and NSCs transplantation can promote the recovery of neurological function by promoting the proliferation, migration, and differentiation of NSCs, and the effect of TMP combined with NSCs transplantation is superior. The mechanism of action may be related to the activation of the Nrf2/HO-1/CXCR4 pathway.

Objectives: To observe the effect of electroacupuncture (EA) at "Baihui" (GV20) and "Shenting" (GV24) on the rats' behavior and the transforming precursor of brain-derived neurotrophic factor (proBDNF) into mature brain-derived neurotrophic factor (mBDNF) in the hippocampus of rats with learning and memory impairment induced by cerebral ischemia-reperfusion (IR), so as to explore its mechanisms underlying improvement of learning and memory ability., Methods: SD rats were randomly divided into blank, sham operation, model, and EA groups, with 6 rats in each group. The model of IR was established by occlusion of the middle cerebral artery. EA (1 Hz/20 Hz) was applied to GV24 and GV20 for 30 min, once daily for 14 days. The neurological function was evaluated according to the Zea Longa's score criteria 24 h after modeling and after intervention. Morris water maze test was used to detect the learning and memory function of the rats. TTC staining was used to evaluate the cerebral infarction volume on the affected side. The protein expression levels of proBDNF, mBDNF, tissue plasminogen activator (tPA), tyrosine kinase receptor B (TrkB) and p75 neurotrophin receptor (p75NTR) in hippocampal tissue were detected by Western blot., Results: Compared with the sham operation group, the neurological function score, the percentage of cerebral infarction volume and the expression levels of proBDNF and p75NTR protein in hippocampus were increased ( P <0.01), while the times of crossing the original platform and the total distance in the target quadrant, the expression levels of mBDNF, TrkB and tPA protein and the ratio of mBDNF/proBDNF were decreased ( P <0.01, P <0.05) in the model group. Compared with the model group, the neurological function score, the percentage of cerebral infarction volume, and the expression levels of proBDNF and p75NTR protein in hippocampus were decreased ( P <0.01, P <0.05), while the times of crossing the original platform, the total distance in the target quadrant, and the expression levels of mBDNF, TrkB and tPA protein and the ratio of mBDNF/proBDNF were increased ( P <0.05, P <0.01) in the EA group., Conclusions: EA can alleviate learning and memory impairment in IR rats, which may be related to its function in up-regulating the expression of tPA protein and promoting the transformation of proBDNF to mBDNF, thus improving the synaptic plasticity.

Background: Delayed cerebral ischaemia (DCI) is a major cause of morbidity and mortality after aneurysmal subarachnoid haemorrhage (aSAH). Chemical angioplasty (CA) and transluminal balloon angioplasty (TBA) are used to treat patients with refractory vasospasm causing DCI. Multi-modal monitoring including brain tissue oxygenation (PbtO 2 ) is routinely used at this centre for early detection and management of DCI following aSAH. In this single-centre pilot study, we are comparing these two treatment modalities and their effects on PbtO 2 ., Methods: Retrospective case series of patients with DCI who had PbtO 2 monitoring as part of their multimodality monitoring and underwent either CA or TBA combined with CA. PbtO 2 values were recorded from intra-parenchymal Raumedic NEUROVENT-PTO® probes. Data were continuously collected and downloaded as second-by-second data. Comparisons were made between pre-angioplasty PbtO 2 and post-angioplasty PbtO 2 median values (4 h before angioplasty, 4 h after and 12 h after)., Results: There were immediate significant improvements in PbtO 2 at the start of intervention in both groups. PbtO 2 then increased by 13 mmHg in the CA group and 15 mmHg in the TBA plus CA group in the first 4 h post-intervention. This improvement in PbtO 2 was sustained for the TBA plus CA group but not the CA group., Conclusion: Combined balloon plus chemical angioplasty results in more sustained improvement in brain tissue oxygenation compared with chemical angioplasty alone. Our findings suggest that PbtO 2 is a useful tool for monitoring the response to angioplasty in vasospasm., (© 2024. The Author(s).)

Ischemic stroke is a major cerebrovascular disease with high morbidity and mortality rates; however, effective treatments for ischemic stroke-related neurological dysfunction have yet to be developed. In this study, we generated neural progenitor cells from human leukocyte antigen major loci gene-homozygous-induced pluripotent stem cells (hiPSC-NPCs) and evaluated their therapeutic effects against ischemic stroke. hiPSC-NPCs were intracerebrally transplanted into rat ischemic brains produced by transient middle cerebral artery occlusion at either the subacute or acute stage, and their in vivo survival, differentiation, and efficacy for functional improvement in neurological dysfunction were evaluated. hiPSC-NPCs were histologically identified in host brain tissues and showed neuronal differentiation into vGLUT-positive glutamatergic neurons, extended neurites into both the ipsilateral infarct and contralateral healthy hemispheres, and synaptic structures formed 12 weeks after both acute and subacute stage transplantation. They also improved neurological function when transplanted at the subacute stage with γ-secretase inhibitor pretreatment. However, their effects were modest and not significant and showed a possible risk of cells remaining in their undifferentiated and immature status in acute-stage transplantation. These results suggest that hiPSC-NPCs show cell replacement effects in ischemic stroke-damaged neural tissues, but their efficacy is insufficient for neurological functional improvement after acute or subacute transplantation. Further optimization of cell preparation methods and the timing of transplantation is required to balance the efficacy and safety of hiPSC-NPC transplantation.

Background: Remote ischemic conditioning has been found to be effective in improving functional outcomes in acute ischemic stroke. We conducted a post hoc analysis of the RICAMIS (Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) trial to determine whether long-term remote ischemic conditioning duration after stroke onset is associated with better clinical outcomes in ischemic stroke., Methods and Results: Patients from the full analysis set were included in this secondary analysis. The primary outcome was the proportion of patients with an excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. Among the 1776 patients, there were 55 patients in the 1 to 7 days remote ischemic conditioning group, 345 in the 8 to 10 days group, 412 in the 11 to 13 days group, 51 in the 14 to 16 days group, and 913 in the control group. Compared with the control group, a significantly higher proportion of excellent functional outcomes at 90 days was found in the 11 to 13 days remote ischemic conditioning group (adjusted absolute difference, 9.1% [95% CI, 3.7%-14.5%]; P  =0.001), which was attenuated in the other groups (adjusted absolute difference in the 8-10 days group, 2.0% [95% CI, -4.0% to 8.0%]; P =0.51; adjusted absolute difference in the 14-16 days group, 7.4% [95% CI, -5.8% to 20.5%]; P =0.27), but compared to the control group, there was lower proportion of excellent functional outcomes in the 1 to 7 days group (adjusted absolute difference, -14.4% [95% CI, -27.8% to 0.0%]; P =0.05)., Conclusions: Among patients with acute moderate ischemic stroke, a higher likelihood of excellent clinical outcome was found in patients with longer duration of remote ischemic conditioning.

Purpose: This study aimed to develop and evaluate a machine learning model and a novel clinical score for predicting outcomes in stroke patients undergoing endovascular thrombectomy., Materials and Methods: This retrospective study included all patients aged over 18 years with an anterior circulation stroke treated at a thrombectomy centre from 2010 to 2020 with external validation. The primary outcome was day 90 mRS ≥3. Existing clinical scores (SPAN and PRE) and Machine Learning (ML) models were compared. A novel clinical score (iSPAN) was derived by adding an optimised weighting of the most important ML features to the SPAN., Results: 812 patients were initially included (397 female, average age 73), 63 for external validation. The best performing clinical score and ML model were SPAN and XGB (sensitivity, specificity and accuracy 0.290, 0.967, 0.628 and 0.693, 0.783, 0.738 respectively). A significant difference was found overall and our XGB model was more accurate than SPAN (p < 0.0018). The most important features were Age, mTICI and total number of passes. The addition of 11 points for mTICI of ≤2B and 3 points for ≥3 passes to the SPAN achieved the best accuracy and was used to create the iSPAN. iSPAN was not significantly less accurate than our XGB model (p > 0.5). In the external validation set, iSPAN and SPAN achieved sensitivity, specificity, and accuracy of (0.735, 0.862, 0.79) and (0.471, 0.897, 0.67) respectively., Conclusion: iSPAN incorporates machine-derived features to achieve better predictions compared to existing clinical scores. It is not inferior to our XGB model and is externally generalisable., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)