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Objective: For patients presenting with acute ischemic stroke (AIS) caused by large vessel occlusions (LVO), mechanical thrombectomy (MT) is the treatment standard of care in eligible patients. Modified Thrombolysis in Cerebral Infarction (mTICI) grades of 2b, 2c, and 3 are all considered successful reperfusion; however, recent studies have shown achieving mTICI 2c/3 leads to better outcomes than mTICI 2b. This study aims to investigate whether any baseline preprocedural or periprocedural parameters are predictive of achieving mTICI 2c/3 in successfully recanalized LVO patients., Methods: We conducted a retrospective multicenter cohort study of consecutive patients presenting with AIS caused by a LVO from 1 January 2017 to 1 January 2023. Baseline and procedural data were collected through chart review. Univariate and multivariate analysis were applied to determine significant predictors of mTICI 2c/3., Results: A total of 216 patients were included in the study, with 159 (73.6%) achieving mTICI 2c/3 recanalization and 57 (26.4%) achieving mTICI 2b recanalization. We found that a higher groin puncture to first pass time (OR = 0.976, 95%CI: 0.960-0.992, p = 0.004), a higher first pass to recanalization time (OR = 0.985, 95%CI: 0.972-0.998, p = 0.029), a higher admission NIHSS (OR = 0.949, 95%CI: 0.904-0.995, p = 0.031), and a lower age (OR = 1.032, 95%CI: 1.01-1.055, p = 0.005) were associated with a decreased probability of achieving mTICI 2c/3., Interpretation: A lower groin puncture to first pass time, a lower first pass to recanalization time, a lower admission NIHSS, and a higher age were independent predictors of mTICI 2c/3 recanalization., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background and Purpose: Acute ischemic stroke due to large vessel occlusion (AIS-LVO) is a major cause of functional dependence. Collateral status (CS) is an important determinant of functional outcomes. Pretreatment CT perfusion (CTP) parameters serve as reliable surrogates of CS. Penumbra Salvage Index (PSI) is another parameter predictive of functional outcomes in AIS-LVO. The aim of this study is to assess the relationship of pretreatment CTP parameters with PSI., Methods: In this prospectively collected, retrospectively reviewed multicenter analysis, inclusion criteria were as follows: (1) CT angiography confirmed middle cerebral artery (MCA) M1-segment and proximal M2-segment occlusion from 9/1/2017 to 9/22/2022; (2) diagnostic CTP; and (3) available diagnostic Magnetic resonance Imaging (MRI) diffusion-weighted images. Pearson correlation analysis was performed to assess the association between cerebral blood volume (CBV) index and hypoperfusion intensity ratio (HIR) with PSI. p value ≤.05 was considered statistically significant., Results: In total, 131 patients (n = 86, M1 and n = 45, proximal M2 occlusion) met our inclusion criteria. CBV index showed a modest positive correlation with PSI (r = 0.34, p<.001) in patients with proximal MCA occlusion. Similar trends were noted in subgroup analysis of patients with M1 occlusion, and proximal M2 occlusion. Whereas, HIR did not have a strong trend or correlation with PSI., Conclusion: CBV index correlates with PSI, whereas HIR does not. Future studies are needed to expand our understanding of the adjunct role of CBV index with other similar pretreatment CTP-based markers in clinical evaluation and decision-making in patients with MCA occlusion., (© 2023 American Society of Neuroimaging.)

Background and Purpose: Quantitative CT perfusion (CTP) thresholds for assessing the extent of ischemia in patients with acute ischemic stroke (AIS) have been established; relative cerebral blood flow (rCBF) <30% is typically used for estimating estimated ischemic core volume and T max (time to maximum) >6 seconds for critical hypoperfused volume in AIS patients with large vessel occlusion (LVO). In this study, we aimed to identify the optimal threshold values for patients presenting with AIS secondary to distal medium vessel occlusions (DMVOs)., Methods: In this retrospective study, consecutive AIS patients with anterior circulation DMVO who underwent pretreatment CTP and follow-up MRI/CT were included. The CTP data were processed by RAPID (iSchemaView, Menlo Park, CA) to generate estimated ischemic core volumes using rCBF <20%, <30%, <34%, and <38% and critical hypoperfused volumes using T max (seconds) >4, >6, >8, and >10. Final infarct volumes (FIVs) were obtained from follow-up MRI/CT within 5 days of symptom onset. Diagnostic performance between CTP thresholds and FIV was assessed in the successfully and unsuccessfully recanalized groups., Results: Fifty-five patients met our inclusion criteria (32 female [58.2%], 68.0 ± 12.1 years old [mean ± SD]). Recanalization was attempted with intravenous tissue-type plasminogen activator and mechanical thrombectomy in 27.7% and 38.1% of patients, respectively. Twenty-five patients (45.4%) were successfully recanalized. In the successfully recanalized patients, no CTP threshold significantly outperformed what is used in LVO setting (rCBF < 30%). All rCBF CTP thresholds demonstrated fair diagnostic performances for predicting FIV. In unsuccessfully recanalized patients, all T max CTP thresholds strongly predicted FIV with relative superiority of T max >10 seconds (area under the receiver operating characteristic curve = .875, p = .001)., Conclusion: In AIS patients with DMVOs, longer T max delays than T max  > 6 seconds, most notably, T max  > 10 seconds, best predict FIV in unsuccessfully recanalized patients. No CTP threshold reliably predicts FIV in the successfully recanalized group nor significantly outperformed rCBF < 30%., (© 2023 American Society of Neuroimaging.)

Competing Interests: DF declares grant support from the US National Institutes of Health and book royalties from Elsevier. FG declares no competing interests.

Background: Neonatal stroke affects 1 in 2800 live births and is a major cause of neurological injury. The Sonic hedgehog (Shh) signaling pathway is critical for central nervous system (CNS) development and has neuroprotective and reparative effects in different CNS injury models. Previous studies have demonstrated beneficial effects of small molecule Shh-Smoothened agonist (SAG) against neonatal cerebellar injury and it improves Down syndrome-related brain structural deficits in mice. Here we investigated SAG neuroprotection in rat models of neonatal ischemia-reperfusion (stroke) and adult focal white matter injury., Methods: We used transient middle cerebral artery occlusion at P10 and ethidium bromide (EB) injection in adult rats to induce damage. Following surgery and SAG or vehicle treatment, we analyzed tissue loss, cell proliferation and fate, and behavioral outcome., Results: We report that a single dose of SAG administered following neonatal stroke preserved brain volume, reduced gliosis, enhanced oligodendrocyte progenitor cell (OPC) and EC proliferation, and resulted in long-term cognitive improvement. Single-dose SAG also promoted proliferation of OPCs following focal demyelination in the adult rat., Conclusions: These findings indicate benefit of one-time SAG treatment post insult in reducing brain injury and improving behavioral outcome after experimental neonatal stroke., Impact: A one-time dose of small molecule Sonic hedgehog agonist protected against neonatal stroke and improved long-term behavioral outcomes in a rat model. This study extends the use of Sonic hedgehog in treating developing brain injury, previously shown in animal models of Down syndrome and cerebellar injury. Sonic hedgehog agonist is one of the most promising therapies in treating neonatal stroke thanks to its safety profile and low dosage., (© 2021. The Author(s).)

Objective: Stroke is a major cause of death and disability in the United States. Current acute stroke therapy consists of clot-dissolving drugs, catheter-based interventions and physical rehabilitation. To date, there are no therapies that directly enhance neuronal survival after a stroke. Previous work from our lab demonstrated that Interleukin-15 (IL-15) peptide could rescue cardiomyocytes subjected to hypoxia. We sought to extend these findings to cortical neurons since IL-15 has been implicated to have an important role in neuronal homeostasis., Methods: We have evaluated the effect of IL-15 peptide on primary cortical neurons derived from embryonic rats in vitro under conditions of anoxia and glucose deprivation, and in vivo following middle cerebral artery occlusion., Results: IL-15 administration rescued neuronal cells subjected to anoxia coupled with glucose deprivation (AGD), as well as with reoxygenation. A hallmark of stroke is the ischemic microenvironment and associated oxidative stress, which results in DNA damage and ER stress, both of which contribute to neuronal cell damage and death. The expression of anoxia, ER stress, and DNA damage factors/markers was evaluated via western blot and correlated with the cellular survival effects of IL-15 in vitro. In addition, IL-15 effect of alleviating ER stress and increasing cell survival was also observed in vivo., Interpretation: Our data indicate, for the first time, that administration of the pleiotropic factor IL-15 reduces neuronal cell death during AGD, which correlates with modulation of multiple cellular stress pathways., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Perinatal stroke is a common cause of life-long neurobehavioral compromise. Mesenchymal stromal cells (MSCs) and EPO (erythropoietin) have each demonstrated short-term benefit with delayed administration after stroke, and combination therapy may provide the most benefit. The purpose of this study is to determine the long-term histological and functional efficacy of enhanced, intranasal stem cell therapy (MSC preexposed to EPO) compared with standard MSC or multidose systemic EPO., Methods: Transient middle cerebral artery occlusion or sham surgery was performed in postnatal day (P) 10 Sprague-Dawley rats, who were treated with single-dose intranasal MSC, MSC preexposed to EPO (MSC/EPO), multidose systemic EPO (EPO3; 1000 u/kg per dose×3 every 72 hours), or cell-conditioned media on P13 (day 3 [P13-P19] for EPO), or on P17 (day 7 [P17-P23] for EPO). At 2 months of age, animals underwent novel object recognition, cylinder rearing, and open field testing to assess recognition memory, sensorimotor function, and anxiety in adulthood., Results: MSC, MSC/EPO, and EPO3 improved brain volume when administered at 3 or 7 days after middle cerebral artery occlusion. MSC/EPO also enhanced long-term recognition memory with either day 3 or day 7 treatment, but EPO3 had the most long-term benefit, improving recognition memory and exploratory behavior and reducing anxiety., Conclusions: These data suggest that single-dose MSC/EPO and multidose systemic EPO improve long-term neurobehavioral outcomes even when administration is delayed, although EPO was the most effective treatment overall. It is possible that EPO represents a final common pathway for improved long-term repair, although the specific mechanisms remain to be determined.

A number of animal models have been used to study hypoxic-ischemic injury, traumatic injury, global hypoxia, or permanent ischemia in both the immature and mature brain. Stroke occurs commonly in the perinatal period in humans, and transient ischemia-reperfusion is the most common form of stroke in neonates. The reperfusion phase is a critical component of injury progression, which occurs over a period of days to weeks, and of the endogenous response to injury. This postnatal day 10 (p10) rat model of transient middle cerebral artery occlusion (tMCAO) creates a unilateral, non-hemorrhagic focal ischemia-reperfusion injury that can be utilized to study the mechanisms of focal injury and repair in the full-term-equivalent brain. The injury pattern that is produced by tMCAO is consistent and highly reproducible and can be confirmed with MRI or histological analyses. The severity of injury can be manipulated through changes in occlusion time and other methods that will be discussed.

Background and Purpose: Stroke is a major cause of neonatal morbidity, often with delayed diagnosis and with no accepted therapeutic options. The purpose of this study is to investigate the efficacy of delayed initiation of multiple dose erythropoietin (EPO) therapy in improving histological and behavioral outcomes after early transient ischemic stroke., Methods: 32 postnatal day 10 (P10) Sprague-Dawley rats underwent sham surgery or transient middle cerebral artery occlusion (tMCAO) for 3h, resulting in injury involving the striatum and parieto-temporal cortex. EPO (1000U/kg per dose×3 doses) or vehicle was administered intraperitoneally starting one week after tMCAO (at P17, P20, and P23). At four weeks after tMCAO, sensorimotor function was assessed in these four groups (6 vehicle-sham, 6 EPO-sham, 10 vehicle-tMCAO and 10 EPO-tMCAO) with forepaw preference in cylinder rearing trials. Brains were then harvested for hemispheric volume and Western blot analysis., Results: EPO-tMCAO animals had significant improvement in forepaw symmetry in cylinder rearing trials compared to vehicle-tMCAO animals, and did not differ from sham animals. There was also significant preservation of hemispheric brain volume in EPO-tMCAO compared to vehicle-tMCAO animals. No differences in ongoing cell death at P17 or P24 were noted by spectrin cleavage in either EPO-tMCAO or vehicle-tMCAO groups., Conclusions: These results suggest that delayed EPO therapy improves both behavioral and histological outcomes at one month following transient neonatal stroke, and may provide a late treatment alternative for early brain injury., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Greater attention has been directed to endovascular recanalization of acute ischemic stroke in septuagenarians and above., Technique: A retrospective chart review was conducted to include patients treated for acute ischemic stroke from 2006 to 2012. All patients underwent initial neurological assessment and non-contrast head CT. Patients treated from 2009 to 2012 additionally received emergent CT angiogram and CT perfusion. 51 patients met the clinical and radiographic criteria and underwent multimodal endovascular revascularization for acute ischemic events., Results: All patients underwent cerebral angiography and met angiographic criteria for endovascular thrombolysis. 34 patients (67%) were older than 80 years of age. 23 patients (45%) received intravenous tissue plasminogen activator prior to admission. Eight (16%) patients underwent stent placement after intra-arterial thrombolysis, 10 (20%) underwent balloon angioplasty and seven (14%) underwent both angioplasty and stent placement. 21 (41%) required only intra-arterial thrombolytics. An improvement in Thrombolysis in Myocardial Infarction score was noted in 34 patients (67%). The average modified Rankin Scale score on discharge was 3.9. Symptomatic intracranial hemorrhage occurred in three patients (6%); none required surgery. One patient (1.9%) had a postoperative retroperitoneal hematoma, which was managed conservatively. Two fatalities resulted from intraoperative vessel rupture (3.9%), with a combined morbidity and mortality of 27.5%., Conclusions: Multimodal endovascular recanalization of acute ischemic stroke is a relatively safe treatment option in patients older than 75 years of age. Careful patient selection by clinical and radiographic inclusion criteria is necessary for the successful management of stroke in this age group.

Background and Purpose: Stroke is a common cause of neonatal brain injury. The subventricular zone is a lifelong source of newly generated cells in rodents, and erythropoietin (EPO) treatment has shown benefit in different animal models of brain injury. The purpose of this study is to investigate the specific role of exogenous EPO on subventricular zone progenitor cell populations in response to neonatal stroke., Methods: Intraventricular injections of green fluorescent protein (GFP)-expressing lentivirus to label subventricular zone precursor cells were made in postnatal day 1 (P1) Long-Evans rats, which then underwent transient middle cerebral artery occlusion on P7. Middle cerebral artery occlusion and sham rats were treated with either vehicle or EPO (1000 U/kg) at reperfusion, 24 hours, and 7 days later. The density of double-labeled DCx+/GFP+, NeuN+/GFP+, O4+/GFP+, GFAP+/GFP+, as well as single-labeled GFP+ and Ki67+ cells, was calculated to determine cell fate outcome in the striatum at 72 hours and 2 weeks after stroke., Results: There was a significant increase in DCx+/GFP+ and NeuN+/GFP+ neurons and O4+/GFP+ oligodendrocyte precursors, with decreased GFAP+/GFP+ astrocytes at both time points in EPO-middle cerebral artery occlusion animals. There was also a significant increase in GFP+ cells and Ki67+ proliferating cells in EPO compared with vehicle-middle cerebral artery occlusion animals., Conclusions: These data suggest that subventricular zone neural progenitor cells proliferate and migrate to the site of injury after neonatal stroke and multiple doses of EPO, with a shift in cell fate toward neurogenesis and oligodendrogliosis at both early and late time points. The contribution of local cell proliferation and neurogenesis remains to be determined.

Introduction: Complications of cranioplasty are known to include infection, wound breakdown, intracerebral hemorrhage, bone resorption, and status epilepticus. Intracerebral hemorrhagic infarction after a cranioplasty is a very rare complication with only 2 reported cases to date. We present the first case in the literature of both supratentorial and infratentorial hemorrhagic infarctions after a cranioplasty., Case Report: A 64-year-old male at an outside hospital suffered a right MCA hemorrhagic infarction requiring decompressive hemicraniectomy. One year later, the patient presents to our hospital for elective right-sided cranioplasty. The procedure was uneventful. However, postoperatively, the patient suffered a generalized tonic-clonic seizure and remained comatose. Electroencephalography showed no signs of status epilepticus, but imaging did reveal diffuse cerebral edema and both infratentorial and supratentorial hemorrhagic infarcts requiring placement of a ventriculostomy, removal of the cranioplasty plate, and suboccipital craniectomy. Postoperative tests revealed only the known right M1 occlusion, with no evidence of venous thrombosis, embolic source for new strokes, or new arterial dissection or occlusion. The patient remained with only brainstem reflexes and eventually expired., Conclusions: This is the first in the literature to report the complication of both supratentorial and infratentorial strokes after a cranioplasty procedure. Reperfusion, vessel injury, and venous stasis after cranioplasty as evaluated by multiple neurological imaging modalities are examined as possible mechanisms for this unique complication. These factors must be considered when evaluating the safety of the procedure for a patient.

Objective: To investigate the effects of neonatal stroke on progenitor cells lining the lateral ventricles., Methods: Intraventricular injection of replication-incompetent green fluorescent protein (GFP)-expressing lentivirus was performed in postnatal day 1 (P1) rats to specifically label radial glia/type B neural stem cells and ependymal cells of the lateral ventricle. A subset of animals was exposed to transient middle cerebral artery occlusion (MCAO) at P7, with mild or moderate injury confirmed by diffusion-weighted MRI and histology. Newborn cells were identified by GFP expression, location and expression of cell type-specific markers in the striatum, cortex and olfactory bulb using confocal microscopy and systematic random sampling., Results: Three weeks lentiviral GFP transduction of cells in the lateral ventricle, abundant GFP-expressing neurons and glia were identified in the rostral migratory stream, olfactory bulb and striatum as expected from labeling the subventricular zone (SVZ) type B neural stem cell lineage. Two weeks following mild or severe focal stroke at P7, no GFP-expressing neurons were detected in striatum or cortex although some single-labeled doublecortin+ immature neurons were detected in the penumbra. The densities of GFP+/ glial fibrillary acidic protein (GFAP)+ astrocytes and GFP+/O4+ oligodendrocytes were reduced in the striatum following MCAO (4.8 +/- 1.02 vs. 2.5 +/- 0.4 cells/high-power field, HPF; p = 0.005; 2.8+/- 1 vs. 0.5 +/- 0.2 cells/HPF, p = 0.008). Furthermore, there was a reduction of GFP+ cells in the olfactory bulb following MCAO (58.8 +/- 14.9 vs. 19.6 +/- 5.4 cells/HPF, p = 0.025). Finally, there was an increased percentage of GFP+/GFAP+ cells (70 vs. 50%), with a decreased proportion of GFP+/O4+ cells (14 vs. 30%) in injured animals., Conclusion: Neurogenesis originating from cells of the lateral ventricle, including SVZ type B cells, is significantly reduced following neonatal stroke. Furthermore, neonatal stroke disrupts gliogenesis in the striatum, decreasing overall numbers of new glia and shifting the population towards astrocytes., (Copyright 2010 S. Karger AG, Basel.)

Neonatal stroke leads to mortality and severe morbidity, but there is no effective treatment currently available. Erythropoietin (EPO) has been shown to promote cytoprotection and neurogenesis and decrease subventricular zone morphologic changes following brain injury. The long-term cellular response to EPO has not been defined, and local changes in cell fate decision may play a role in functional improvement. We performed middle cerebral artery occlusion in P10 rats. EPO treatment (5 U/g i.p.) significantly preserved hemispheric brain volume 6 weeks after injury. Furthermore, EPO increased the percentage of newly generated neurons while decreasing newly generated astrocytes following brain injury, without demonstrating long-term differences in the subventricular zone. These results suggest that EPO may neuroprotect and direct cell fate toward neurogenesis and away from gliogenesis in neonatal stroke., (2007 S. Karger AG, Basel)

As the resident macrophages of the brain and spinal cord, microglia are crucial for the phagocytosis of infectious agents, apoptotic cells and synapses. During brain injury or infection, bone-marrow derived macrophages invade neural tissue, making it difficult to distinguish between invading macrophages and resident microglia. In addition to circulation-derived monocytes, other non-microglial central nervous system (CNS) macrophage subtypes include border-associated meningeal, perivascular and choroid plexus macrophages. Using immunofluorescent labeling, flow cytometry and Cre-dependent ribosomal immunoprecipitations, we describe P2ry12-CreER, a new tool for the genetic targeting of microglia. We use this new tool to track microglia during embryonic development and in the context of ischemic injury and neuroinflammation. Because of the specificity and robustness of microglial recombination with P2ry12-CreER, we believe that this new mouse line will be particularly useful for future studies of microglial function in development and disease.

In human preterm newborns, caffeine increases brain activity and improves neurodevelopmental outcomes. In animal models of hypoxic ischemic brain injury, caffeine pretreatment reduces infarct volume. We studied the relationship between tissue neuroprotection and brain activity after injury to further understand caffeine neuroprotection. Rat dams received caffeine prior to birth or on postnatal day 3 (P3) through P16. Caffeine-treated and -untreated pups underwent the Vannucci procedure (unilateral carotid ligation, global hypoxia) on P2. A subset had EEG recordings. Brain hemispheric infarct volume was measured on P16. P2 hypoxic ischemia (HI) results in histologic brain injury (mean ± standard deviation infarct volume 10.3 ± 4.6%) and transient suppression of EEG activity. Caffeine pretreatment reduces brain injury (mean ± standard deviation infarct volume 1.6 ± 4.5%, p < 0.001) and improves amplitude-integrated EEG (aEEG) and EEG burst duration and amplitude. Caffeine treatment after HI does not reduce infarct volume (mean ± standard deviation 8.3 ± 4.1%, p = 1.0). However, caffeine posttreatment was equally effective at restoring aEEG amplitude and EEG burst duration and amplitude. Thus, caffeine supports brain background electrical activity independent of tissue neuroprotection.

A number of animal models have been used to study hypoxic-ischemic injury, traumatic injury, global hypoxia, or permanent ischemia in both the immature and mature brain. Stroke occurs commonly in the perinatal period in humans, and transient ischemia-reperfusion is the most common form of stroke in neonates. The reperfusion phase is a critical component of injury progression, which occurs over a period of days to weeks, and of the endogenous response to injury. This postnatal day 10 (p10) rat model of transient middle cerebral artery occlusion (tMCAO) creates a unilateral, non-hemorrhagic focal ischemia-reperfusion injury that can be utilized to study the mechanisms of focal injury and repair in the full-term-equivalent brain. The injury pattern that is produced by tMCAO is consistent and highly reproducible and can be confirmed with MRI or histological analyses. The severity of injury can be manipulated through changes in occlusion time and other methods that will be discussed.

Background and purposeStroke is a major cause of neonatal morbidity, often with delayed diagnosis and with no accepted therapeutic options. The purpose of this study is to investigate the efficacy of delayed initiation of multiple dose erythropoietin (EPO) therapy in improving histological and behavioral outcomes after early transient ischemic stroke.Methods32 postnatal day 10 (P10) Sprague-Dawley rats underwent sham surgery or transient middle cerebral artery occlusion (tMCAO) for 3h, resulting in injury involving the striatum and parieto-temporal cortex. EPO (1000U/kg per dose×3 doses) or vehicle was administered intraperitoneally starting one week after tMCAO (at P17, P20, and P23). At four weeks after tMCAO, sensorimotor function was assessed in these four groups (6 vehicle-sham, 6 EPO-sham, 10 vehicle-tMCAO and 10 EPO-tMCAO) with forepaw preference in cylinder rearing trials. Brains were then harvested for hemispheric volume and Western blot analysis.ResultsEPO-tMCAO animals had significant improvement in forepaw symmetry in cylinder rearing trials compared to vehicle-tMCAO animals, and did not differ from sham animals. There was also significant preservation of hemispheric brain volume in EPO-tMCAO compared to vehicle-tMCAO animals. No differences in ongoing cell death at P17 or P24 were noted by spectrin cleavage in either EPO-tMCAO or vehicle-tMCAO groups.ConclusionsThese results suggest that delayed EPO therapy improves both behavioral and histological outcomes at one month following transient neonatal stroke, and may provide a late treatment alternative for early brain injury.

Background: Pretreatment CT Perfusion (CTP) parameters serve as reliable surrogates of collateral status (CS). In this study, we aim to assess the relationship between the novel compensation index (CI, Tmax > 4 s/Tmax > 6 s) and already established CTP collateral markers, namely cerebral blood volume (CBV) index and Hypoperfusion Intensity Ratio (HIR), with the reference standard American Society of Interventional and Therapeutic Neuroradiology (ASITN) collateral score (CS) on DSA. Methods: In this retrospective study, inclusion criteria were the following: (a) CT angiography confirmed anterior circulation large vessel occlusion from 9 January 2017 to 10 January 2023; (b) diagnostic CT perfusion; and (c) underwent mechanical thrombectomy with documented DSA-CS. Student t-test, Mann–Whitney-U-test and Chi-square test were used to assess differences. Spearman's rank correlation and logistic regression analysis were used to assess associations. p ≤ 0.05 was considered significant. Results: In total, 223 patients (mean age: 67.8 ± 15.8, 56% female) met our inclusion criteria. The CI (ρ = 0.37, p < 0.001) and HIR (ρ = −0.29, p < 0.001) significantly correlated with DSA-CS. Whereas the CBV Index (ρ = 0.1, p > 0.05) did not correlate with DSA-CS. On multivariate logistic regression analysis taking into account age, sex, ASPECTS, tPA, premorbid mRS, NIH stroke scale, prior history of TIA, stroke, atrial fibrillation, diabetes mellitus, hyperlipidemia, heart disease and hypertension, only CI was not found to be independently associated with DSA-CS (adjusted OR = 1.387, 95% CI: 1.09–1.77, p < 0.01). Conclusion: CI demonstrates a stronger correlation with DSA-CS compared to both the HIR and CBV Index where it may show promise as an additional quantitative pretreatment CS biomarker. [ABSTRACT FROM AUTHOR]

In recent years, growth factor therapy has emerged as a potential treatment for ischemic brain injury. The efficacy of therapies that either directly introduce or stimulate local production of growth factors and their receptors in damaged brain tissue has been tested in a multitude of models for different Central Nervous System (CNS) diseases. These growth factors include erythropoietin (EPO), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor (IGF-1), among others. Despite the promise shown in animal models, the particular growth factors that should be used to maximize both brain protection and repair, and the therapeutic critical period, are not well defined. We will review current pre-clinical and clinical evidence for growth factor therapies in treating different causes of brain injury, as well as issues to be addressed prior to application in humans. [ABSTRACT FROM AUTHOR]

Background: The role of smooth muscle cell (SMC) phenotypic modulation in the cerebral circulation and pathogenesis of stroke has not been determined. Cigarette smoke is a major risk factor for atherosclerosis, but potential mechanisms are unclear, and its role in SMC phenotypic modulation has not been established. Methods and Results: In cultured cerebral vascular SMCs, exposure to cigarette smoke extract (CSE) resulted in decreased promoter activity and mRNA expression of key SMC contractile genes (SM-α-actin, SM-22α, SM-MHC) and the transcription factor myocardin in a dose-dependent manner. CSE also induced pro-inflammatory/matrix remodeling genes (MCP-1, MMPs, TNF-α, IL-1β, NF-κB). CSE increased expression of KLF4, a known regulator of SMC differentiation, and siKLF4 inhibited CSE induced suppression of SMC contractile genes and myocardin and activation of inflammatory genes. These mechanisms were confirmed in vivo following exposure of rat carotid arteries to CSE. Chromatin immune-precipitation assays in vivo and in vitro demonstrated that CSE promotes epigenetic changes with binding of KLF4 to the promoter regions of myocardin and SMC marker genes and alterations in promoter acetylation and methylation. Conclusion: CSE exposure results in phenotypic modulation of cerebral SMC through myocardin and KLF4 dependent mechanisms. These results provides a mechanism by which cigarette smoke induces a pro-inflammatory/matrix remodeling phenotype in SMC and an important pathway for cigarette smoke to contribute to atherosclerosis and stroke. [ABSTRACT FROM AUTHOR]

Neonatal stroke leads to mortality and severe morbidity, but there currently is no effective treatment. Erythropoietin (EPO) promotes cytoprotection and neurogenesis in the short term following brain injury; however, long-term cognitive outcomes and optimal dosing regimens have not been clarified. We performed middle cerebral artery occlusion in postnatal day 10 rats, which were treated with either a single dose of EPO (5 U/g, i.p.) immediately upon reperfusion, or 3 doses of EPO (1 U/g, i.p. each) at 0 h, 24 h, and 7 days after injury. At 3 months after injury, rats treated with 3 doses of EPO did not differ from shams in the Morris water maze, and generally performed better than either rats treated with a single dose or vehicle-treated injured rats. These multiple-dose-treated rats also had increases in hemispheric volume and its subregions. These results suggest that additional, later doses of EPO may be required for cell repair, proliferation, and long-term incorporation into neural networks after neonatal brain injury. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Hemorrhagic conversion (HC) is a known complication after acute ischemic stroke (AIS) in patients undergoing mechanical thrombectomy (MT). Although symptomatic HC has been shown to lead to poor neurologic outcomes, the effect of asymptomatic HC (aHC) is unclear. This study aims to identify predictors of aHC and to determine the short-term outcomes. This is a single-institution retrospective study of patients with anterior circulation stroke (AIS) who underwent MT between January 2016 and September 2022. Radiographic HC was identified on postoperative imaging. Asymptomatic hemorrhage was defined as no acute neurologic decline attributable to imaging findings. Baseline characteristics, technical aspects, and outcomes were compared between aHC and no-HC groups. Logistic regression and multivariate analysis were performed. A total of 615 patients underwent MT for AIS, of whom 496 met the inclusion criteria. A total of 235 patients (47.4%) had evidence of aHC. Diabetes mellitus (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.06–2.41; P = 0.03), hyperglycemia (OR, 1.01; 95% CI, 1.00–1.01; P = 0.002), greater number of passes (OR, 1.14; 95% CI, 1.00–1.31; P = 0.05), and longer time to reperfusion (OR, 1.02; 95% CI, 1.00–1.05; P = 0.05) were associated with aHC. Patients with aHC were significantly more likely to require rehabilitation, whereas those without HC were more likely to be discharged home (P < 0.001). There were no significant differences in long-term outcomes. HC occurred in up to half of patients who underwent MT for AIS, most of whom were clinically asymptomatic. Despite clinical stability, aHC was significantly associated with a greater need for inpatient rehabilitation. Predictors of aHC included hyperglycemia and a longer time to reperfusion. [ABSTRACT FROM AUTHOR]

Although randomized controlled trials have compared surgery versus endovascular treatment for intracranial aneurysms, the literature is sparse in terms of subgroup analysis for anterior communicating artery (ACoA) aneurysm management. This systematic review and meta-analysis sought to compare surgical versus endovascular treatment for ACoA aneurysms. Medline, PubMed, and Embase were searched from inception to December 12, 2022. Primary outcomes were post-treatment modified Rankin Scale (mRS) >2 and mortality. Secondary outcomes were aneurysm obliteration, retreatment and recurrence, rebleeding, technical failure, vessel rupture, aneurysmal subarachnoid hemorrhage-related hydrocephalus, symptomatic vasospasm, and stroke. Eighteen studies yielded 2368 patients, from which 1196 (50.5%) and 1172 (49.4%) patients underwent surgery and endovascular treatment, respectively. The odds ratio (OR) of mortality was similar in total (OR = 0.92 [0.63–1.37], P = 0.69), ruptured (OR = 0.92 [0.62–1.36], P = 0.66), and unruptured cohorts (OR = 1.58 [0.06–39.60], P = 0.78). The OR of mRS > 2 was similar in total (OR = 0.75 [0.50–1.13], P = 0.17), ruptured (OR = 0.77 [0.49–1.20], P = 0.25), and unruptured cohorts (OR = 0.64 [0.21–1.96], P = 0.44). The OR of obliteration was higher with surgery in the total (OR = 2.52 [1.49–4.27], P = 0.0008) and ruptured cohorts (OR = 2.61 [1.33–5.10], P = 0.005) and unruptured group (OR = 3.46 [1.30–9.20], P = 0.01). The OR of retreatment was lower with surgery in the total (OR = 0.37 [0.17–0.76], P = 0.007) and ruptured cohorts (OR = 0.31 [0.11–0.89], P = 0.03), thought it was similar in the unruptured group (OR = 0.51 [0.08–3.03], P = 0.46). The OR of recurrence was lower with surgery in the total (OR = 0.22 [0.10, 0.47], P = 0.0001), ruptured (OR = 0.16 [0.03, 0.90], P = 0.04), and mixed (un) ruptured cohorts (OR = 0.22 [0.09–0.53], P = 0.0009). The OR of rebleeding in ruptured group was similar (OR = 0.66 [0.29–1.52], P = 0.33). The ORs of other outcomes were similar. ACoA aneurysms may be safely treated with either surgery or endovascular treatment, although microsurgical clipping demonstrates higher obliteration rates and lower rates of retreatment and recurrence. [ABSTRACT FROM AUTHOR]