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Background: Amphetamines possess sympathomimetic properties that can affect cerebral vasculature though conflicting reports exist about their effect on vasospasm risk and clinical outcomes in aneurysmal subarachnoid hemorrhage. This study aimed to characterize the impact of recent amphetamine use on vasospasm development in aneurysmal subarachnoid hemorrhage as well as neurological outcomes. Methods: We retrospectively screened 441 consecutive patients admitted with a diagnosis of subarachnoid hemorrhage who underwent at least one cerebral digital subtraction angiogram. Patients were excluded if no urinary toxicology screen was performed within 24 h of admission, if there was a diagnosis of non-aneurysmal subarachnoid hemorrhage, or if ictus was greater than 72 h from hospital admission. Vasospasm characteristics were collected from digital subtraction angiography and transcranial Doppler studies. Results: 129 patients were included and 24 tested positive for amphetamines on urine drug screen. No significant differences were found in respect to patient age, sex, or admission clinical severity scales (Hunt-Hess and modified Fisher) based on amphetamine use. There was no difference in the severity of vasospasm or time to peak severity based on recent amphetamine use. A trend toward more isolated posterior circulation vasospasm was observed in the amphetamine present group (16.7% vs. 4.8%, p = 0.06), while there was higher incidence of anterior circulation vasospasm in the amphetamine absent group (79.2% vs. 94.3%, p = 0.03). There was no difference in delayed cerebral ischemia incidence, length of hospital stay, need for ventriculoperitoneal shunt placement, functional outcome at discharge or hospital mortality based on amphetamine use. Interpretation: Recent amphetamine use was not associated with worse vasospasm severity or delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage patients. Further investigations about localized effects in the posterior circulation and impact on long-term functional outcomes are warranted. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a major cause of mortality and disability worldwide. Among patients with ischemic stroke, the primary treatment goal is to reduce acute cerebral ischemic injury and limit the infarct size in a timely manner by ensuring effective cerebral reperfusion through the administration of either intravenous thrombolysis or endovascular therapy. However, reperfusion can induce neuronal death, known as cerebral reperfusion injury, for which effective therapies are lacking. Accumulating data supports a paradigm whereby cerebral ischemia/reperfusion (I/R) injury is coupled with impaired mitochondrial function, contributing to the pathogenesis of ischemic stroke. Herein, we review recent evidence demonstrating a heterogeneous mitochondrial response following cerebral I/R injury, placing a specific focus on mitochondrial protein modifications, reactive oxygen species, calcium (Ca2+), inflammation, and quality control under experimental conditions using animal models. [ABSTRACT FROM AUTHOR]

Introduction: Ischemic stroke is a devastating neurovascular condition that occurs when cerebral tissue fails to receive an adequate supply of oxygen. Despite being a leading cause of death and disability worldwide, therapeutic interventions are currently limited. Polyamidoamine (PAMAM) dendrimers are nanomolecules commonly used in biomedical applications due to their ability to encapsulate small-molecules and improve their pharmacokinetic properties. Curcumin is known to have anti-inflammatory and antioxidant effects yet suffers from poor solubility and bioavailability. The purpose of this study is to investigate the efficacy of curcumin encapsulated in PAMAM dendrimers as a potential therapeutic treatment for ischemic stroke by studying post-stroke lesion size, astrocyte reactivity, and functional recovery in a rat model of cerebral ischemia. Methods: Forty-eight male and female Sprague-Dawley rats (280–380 g) underwent either a 90-min middle cerebral artery occlusion (MCAo) or sham surgery before receiving one of four treatments: (1) Hanks' balanced salt solution (HBSS) control, (2) empty dendrimer control, (3) curcumin control, or (4) curcumin encapsulated in PAMAM dendrimer. Neurobehavioral outcomes were evaluated at 1-, 3-, 5-, and 7-day post-surgery, after which animals were euthanized on day 8 to assess infarct volume and GFAP immunoreactivity. Results: Animals that received formulations containing dendrimers (curcumin encapsulated in dendrimers or empty dendrimers) demonstrated significantly lower levels of GFAP immunoreactivity and improved functional recovery, including weight and neurobehavioral scores, compared to the formulations that did not contain dendrimers (curcumin and HBSS control). Additionally, the dendrimer-curcumin treatment group exhibited a significantly improved paw laterality index over the course of the study compared with the other three treatment groups. Conclusion: Although the post-stroke administration of curcumin encapsulated in PAMAM dendrimers modulates the astrocytic response and promotes functional recovery following ischemic stroke in rats, its therapeutic benefits may be driven by PAMAM dendrimers as the empty dendrimer treatment group also showed significant improvements post-stroke. Further investigation regarding PAMAM dendrimers in treating neuroinflammatory conditions remains warranted. [ABSTRACT FROM AUTHOR]

Aneurysmal subarachnoid hemorrhage (aSAH) is a serious condition complicated by delayed cerebral ischemia (DCI), where inflammation plays a key role. Although altered gut permeability is noted in other conditions, its significance in aSAH remains unclear. Fatty acid-binding protein (FABP-I), lipopolysaccharide-binding protein (LBP), and soluble CD-14 (sCD-14) are established markers of barrier dysfunction. This study investigates gut permeability marker changes in early and late aSAH phases. The study included 177 aSAH patients and 100 controls. Serum samples were collected on days 1 (D1) and 9 (D9) after ictus. FABP-I, LBP, and sCD-14 levels were measured via ELISA, and clinical data were recorded. Outcomes were assessed using the 90-day modified Rankin scale (mRS 0–3 = favorable outcome). Serum FABP-I was significantly lower in aSAH patients (p < 0.05), while LBP and sCD-14 were higher (p < 0.001) compared to controls. FABP-I did not differ between outcome groups, but LBP and sCD-14 were significantly elevated in unfavorable outcomes (p < 0.001). These markers differed in patients without in-hospital infection, with higher levels noted in DCI patients during the later phase (p < 0.05). In aSAH patients without infection, differences in LBP and sCD-14 levels between outcome groups suggest potential endotoxin release from microbial systems, contributing to neuroinflammation and influencing outcomes. [ABSTRACT FROM AUTHOR]

Stroke is a major cause of mortality and long-term disability worldwide, making early diagnosis and effective treatment crucial for reducing its impact. In response to the limited efficacy of current treatments, alternative therapeutic strategies, such as novel biomarkers and therapies, are emerging to address this critical unmet medical need. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression at the post-transcriptional level. Due to their dysregulation, they have been implicated in the onset and progression of various diseases. Recent research highlighted the important role of miR-181 family members in the context of stroke. Polymorphisms such as rs322931 in miR-181b are associated with increased stroke risk. miR-181 family members are aberrantly expressed and related to various aspects of stroke pathology, affecting inflammatory responses or neuronal survival. We provide a comprehensive overview of how alterations in miR-181 expression influence stroke mechanisms and their potential as therapeutic targets. [ABSTRACT FROM AUTHOR]

Despite the presentation of similar psychological symptoms, psychological dysfunction secondary to brain injury exhibits markedly lower treatment efficacy compared to injury-independent psychological dysfunction. This gap remains evident, despite extensive research efforts. This review integrates clinical and preclinical evidence to provide a comprehensive overview of the neurobiological mechanisms underlying neuropsychological disorders, focusing on the role of key brain regions in emotional regulation across various forms of brain injuries. It examines therapeutic interventions and mechanistic targets, with the primary goal of identifying pathways for targeted treatments. The review highlights promising therapeutic avenues for addressing injury-associated psychological dysfunction, emphasizing Nrf2, neuropeptides, and nonpharmacological therapies as multi-mechanistic interventions capable of modulating upstream mediators to address the complex interplay of factors underlying psychological dysfunction in brain injury. Additionally, it identifies sexually dimorphic factors as potential areas for further exploration and advocates for detailed investigations into sex-specific patterns to uncover additional contributors to these disorders. Furthermore, it underscores significant gaps, particularly the inadequate consideration of interactions among causal factors, environmental influences, and individual susceptibilities. By addressing these gaps, this review provides new insights and calls for a paradigm shift toward a more context-specific and integrative approach to developing targeted therapies for psychological dysfunction following brain injuries. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke is a major public health concern, contributing significantly to global morbidity and mortality. Recent studies have suggested that alterations in liver enzymes may be linked to the risk of developing a stroke. However, the relationship between liver enzymes and ischemic stroke remains unclear. Objective: To examine the potential role of liver enzymes as biomarkers for ischemic stroke. Methods: We systematically searched four databases for articles investigating the association between liver enzymes and ischemic stroke up to March 20th, 2024. Newcastle Ottawa Scale judged the quality of included studies. Risk ratio (RR), hazard ratio (HR), or odds ratio (OR) were extracted and statistically analyzed by RevMan and R software. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessed the certainty of evidence. Results: Increased levels of gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) have shown statistically significant association with increased ischemic stroke risk (RR: 1.43, 95% CI: [1.30 to 1.57], P > 0.00001) and (RR: 1.60, 95% CI: [1.22 to 2.10], P = 0.0006), respectively. Conversely, increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) showed no significant association with ischemic stroke risk (RR: 0.92, 95% CI: [0.68 to 1.24], P = 0.58) and (RR: 1.43, 95% CI: [0.83 to 2.49], P = 0.20), respectively. The evidence for all outcomes had a low or very low level of certainty. Conclusion: GGT and ALP could be potential biomarkers for increased ischemic stroke risk, which necessitates careful follow-up. However, AST and ALT did not show such association. Key Points: The relationship between liver enzymes and ischemic stroke risk is still unclear. We systematically reviewed and analyzed previously published cohort and case control studies. A significant positive association was found between levels of GGT and ALP enzymes with ischemic stroke risk. No significant association was found between ALT and AST enzymes levels with ischemic stroke risk. Further studies are still needed to investigate the causal relationship between different levels of liver enzymes and the risk of ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Aeromedical transfer of patients with ischemic stroke to access hyperacute stroke treatment is becoming increasingly common. Little is known about how rapid changes of altitude and atmospheric pressure can impact cerebral perfusion and ischemic burden. In patients with ischemic stroke, there is a theoretical possibility that this physiologic response of hypoxia-driven hyperventilation at higher altitude can lead to a relative drop in PaCO2. This would ultimately result in cerebral vasoconstriction, and therefore worsening of the ischemic burden in patients with ischemic stroke. Currently, there are no specific recommendations in stroke guidelines for optimizing altitude of aeromedical transportation to minimize the rate of ischemic burden. In this scoping review, we aim to map the available literature that addressed whether PaCO2 changes with altitude. This would be the steppingstone for more in-depth analyses into the cerebral autoregulatory consequences of high altitude on cerebral ischemia to form future guidelines. Methods and analysis: We will follow scoping review methods recommended by the Joanna Briggs Institute. Electronic databases MEDLINE, Embase, Web of Science, and Cochrane Central Register of Systematic will be systematically searched to identify articles that report on the acute response of PaCO2 on acute change in altitude. Two independent investigators will perform duplicate title and abstract screening and full-text review, followed by duplicate data extraction. We will present quantitative data using descriptive statistics. Key textual information will be synthesized in a tabular format Simple statistics on the frequency of papers, data will be presented via histogram. Ethics and dissemination: This scoping review does not require ethical approval. The results of our scoping review will be published in academic medical journals and presented at medical conferences. The findings will highlight the current availability of literature on PaCO2 changes with altitude. Registration: This scoping review protocol has been registered in Open Science Framework (DOI 10.17605/OSF.IO/UVK83). [ABSTRACT FROM AUTHOR]

Curvature of large arteries in the cervical and intracranial regions represents a common morphological vascular alteration. However, the precise mechanisms underlying its formation and progression remain unclear. Increasing evidence suggests a potential correlation between arterial curvature and ischemic stroke. This manuscript involves a review of the relevant literature that delineates the measurement techniques for assessing arterial curvature, the mechanisms contributing to its formation, and recent evidence linking arterial curvature to stroke. Arterial curvature is primarily influenced by genetic factors, hypertension, sex, and age, and it may indicate weakened arterial walls. Furthermore, the haemodynamic changes associated with arterial curvature can result in reduced cerebral perfusion pressure, endothelial dysfunction, oxidative stress, and inflammatory responses. These factors contribute to the development of atherosclerosis and the formation of arterial dissections. The degree of arterial curvature may serve as a risk factor for cerebral ischemia, alongside traditional vascular risk factors. Further investigation into arterial curvature could yield valuable insights for clinicians managing patients with curved vessels. [ABSTRACT FROM AUTHOR]

Ischemic stroke (IS), accounting for 87 % of stroke incidences, constitutes a paramount health challenge owing to neurological impairments and irreversible tissue damage arising from cerebral ischemia. Chief among therapeutic obstacles are the restrictive penetration of the blood-brain barrier (BBB) and insufficient targeting precision, hindering the accumulation of drugs in ischemic brain areas. Motivated by the remarkable capabilities of natural membrane-based delivery vehicles in achieving targeted delivery and traversing the BBB, thanks to their biocompatible architecture and bioactive components, numerous membrane-engineered systems such as cells, cell membranes and extracellular vesicles have emerged as promising platforms to augment IS treatment efficacy with the help of nanotechnology. This review consolidates the primary pathological manifestations following IS, elucidates the unique functionalities of natural membrane drug delivery systems (DDSs) with nanotechnology, as well as delineates the structural characteristics of various natural membranes alongside rational design strategies employed. The review illuminates both the potential and challenges encountered when employing natural membrane DDSs in IS drug therapy, offering fresh perspectives and insights for devising efficacious and practical delivery systems tailored to IS intervention. An overview of the latest trends in the development and application potential of drug delivery systems based on natural membranes inspired by cells for treating ischemic stroke, and focusing on the natural membrane structure to explore its advantages of constructing a biomimetic drug delivery system and expand its engineering methods based on natural membrane from wide sources and characterization of the ischemic microenvironment. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Cerebral ischemic strokes cause brain damage, primarily through inflammatory factors. One of the regions most affected by middle cerebral artery occlusion (MCAO) is the hippocampus, specifically the CA1 area, which is highly susceptible to ischemia. Previous studies have demonstrated the anti-inflammatory properties of quercetin. Therefore, this study aimed to investigate the neuroprotective effects of quercetin on hippocampal CA1 neurons following MCAO. Materials and methods: Fifty-six male Albino Wistar rats were divided into seven groups (intact, sham, stroke, vehicle, and three quercetin-treated groups receiving 5, 10, and 20 mg/kg, respectively), each containing 8 rats. Various assessments, including brain water content, the rotarod test, the Bederson neurological score, the Morris water maze (MWM) test, the shuttle box test, histopathological evaluations, and measurements of interleukin-10 (IL-10) and interleukin-1β (IL-1β) levels, were conducted across the groups. Results: Compared with control rats, 5 and 10 mg/kg quercetin-treated rats presented significant improvements in brain water content, neurological function, and motor function and improved performance in the MWM and shuttle box tests. Histopathological analyses revealed better preservation of CA1 neurons in these groups. Additionally, IL-10 levels significantly increased, whereas IL-1β levels significantly decreased. However, the group receiving 20 mg/kg quercetin showed no statistically significant changes in the parameters assessed (P > 0.05). Conclusion: Quercetin may help prevent or ameliorate brain injuries caused by acute stroke, suggesting its neuroprotective effects. The reduction in IL-1β and increase in IL-10 may play key roles in quercetin's protective mechanism. [ABSTRACT FROM AUTHOR]

Stroke is the leading cause of death and disability worldwide, with ischemic stroke accounting for the majority of these. HBA is the active ingredient in Gastrodia elata and has potential therapeutic effects on central nervous system diseases. In this study, the cell model of cerebral ischemia was replicated by the culture method of oxygen-glucose deprivation/reoxygenation, and the rat model of vascular dementia was established by the two-vessel occlusion method. Metabolomics technology was employed to analyze the metabolic changes in ischemic neurons induced by HBA, and potential therapeutic targets were verified. The protective effects of HBA on ischemic neurons and their mitochondria were examined through multiple indicators, and the related mechanisms were verified. HBA can improve post-ischemic cognitive impairment in rats, and its mechanism is related to the regulation of the choline-activated phospholipase D2/Sirtuin 1/peroxisome proliferator-activated receptor-γ coactivator 1α pathway to improve mitochondrial function and reduce autophagic activity to maintain mitochondrial homeostasis. It is concluded that HBA has a protective effect on neuronal damage and cognitive impairment caused by cerebral ischemia by regulating key metabolites and signaling pathways, and that it provides a new molecular target for the treatment of cerebral ischemia. [ABSTRACT FROM AUTHOR]

Brain ischemia causes disruption in cerebral blood flow and blood–brain barrier integrity, which are normally maintained by astrocyte endfeet. Emerging evidence points to dysregulation of the astrocyte translatome during ischemia, but its effects on the endfoot translatome are unknown. In this study, we aimed to investigate the early effects of ischemia on the astrocyte endfoot translatome in a rodent cerebral ischemia and reperfusion model of stroke. To do so, we immunoprecipitated astrocyte-specific tagged ribosomes (RiboTag IP) from mechanically isolated brain microvessels. In mice subjected to middle cerebral artery occlusion and reperfusion and contralateral controls, we sequenced ribosome-bound RNAs from perivascular astrocyte endfeet and identified 205 genes that were differentially expressed in the endfoot translatome after ischemia. The main biological processes associated with these differentially expressed genes included proteostasis, inflammation, cell cycle/death, and metabolism. Transcription factors whose targets were enriched amongst upregulated translating genes included HSF1, the master regulator of the heat shock response. The most highly upregulated genes in the translatome were HSF1-dependent Hspa1a and Hspa1b, which encode the inducible HSP70. Using qPCR, Western blot, and immunohistochemistry, we confirmed that HSP70 is upregulated in astrocyte endfeet after ischemia. This coincided with an increase in ubiquitination across the proteome that suggests that ischemia induces a disruption in proteostasis in astrocyte endfeet. These findings suggest a robust proteostasis response to proteotoxic stress in the endfoot translatome after ischemia. Modulating proteostasis in endfeet may be a strategy to preserve endfoot function and BBB integrity after ischemic stroke. [ABSTRACT FROM AUTHOR]

Objective(s): Anemoside B4 (AB4) is a multifunctional compound with anti-inflammatory, antiapoptotic, anti-oxidant, antiviral, and autophagy-enhancing effects. However, the role of AB4 in cerebral ischemia/reperfusion injury (CIRI) remains obscure. This experiment aims to investigate the pharmacological effects of AB4 in CIRI. Materials and Methods: In vivo, eighty male SD rats were randomly divided into five groups: sham, MCAO/R, LD group (2.5 mg/kg), MD group (5 mg/kg), and HD group (10 mg/kg). The rats in sham and MCAO/R groups were given equal volumes of normal saline. In vitro, PC12 cells were divided into five groups: normal, OGD/R, OGD/R+AB4 (50 μM), OGD/R+AB4 (100 μM), and OGD/R+AB4 (200 μM). The cells were treated with hypoxia and hypoglycemia for 1.5 hr and reoxygenation for 24 hr. Results: In vivo, TTC and neurological scoring tests indicated that AB4 favors promoting the recovery of the brain. The histopathologic study of the brain tissues revealed that AB4 inhibited the damage of neuron cells. The TUNEL assay found that AB4 could improve cell apoptosis and prevent the brain from injury. In vitro, the data showed that AB4 inhibited cell damage and prevented PC12 cells from OGD/R injury, reduced IL-1β content, and increased the IL-10 level. AB4 could inhibit apoptosis of PC12 cells, down-regulate Caspase 12 and BAX expression, and up-regulate Bcl-2 expression. Conclusion: AB4 played a protective role in CIRI and could be a promising active ingredient against ischemia stroke. [ABSTRACT FROM AUTHOR]

Although ischemia increases the abundance of plasminogen activator inhibitor-1 (PAI-1), its source and role in the ischemic brain remain unclear. We detected PAI-1-immunoreactive cells with morphological features of reactive astrocytes in the peri-ischemic cortex of mice after an experimentally-induced ischemic lesion, and of a chimpanzee that suffered a naturally-occurring stroke. We found that although the abundance of PAI-1 increases 24 hours after the onset of the ischemic injury in a non-reperfusion murine model of ischemic stroke, at that time-point there is no difference in astrocytic reactivity and the volume of the ischemic lesion between wild-type (Wt) animals and in mice either genetically deficient (PAI-1−/−) or overexpressing PAI-1 (PAI-1Tg). In contrast, 72 hours later astrocytic reactivity and the volume of the ischemic lesion were decreased in PAI-1−/− mice and increased in PAI-1Tg animals. Our immunoblottings and fractal analysis studies show that the abundance of astrocytic PAI-1 rises during the recovery phase from a hypoxic injury, which in turn increases the abundance of glial fibrillary acidic protein (GFAP) and triggers morphological features of reactive astrocytes. These studies indicate that cerebral ischemia-induced release of astrocytic PAI-1 triggers astrocytic reactivity associated with enlargement of the necrotic core. [ABSTRACT FROM AUTHOR]

Purpose: In the brain imaging based on electrical impedance tomography, it is sometimes not able to attach 16 electrodes due to space restriction caused by craniotomy. As a result of this, the number of boundary measurements decreases, and spatial resolution of reconstructed conductivity distribution is reduced. The purpose of this study is to enhance reconstruction quality in cases of limited measurement. Design/methodology/approach: A new data expansion method based on the shallow convolutional neural network is proposed. An eight-electrode model is built from which fewer boundary measurements can be obtained. To improve the imaging quality, shallow convolutional neural network is constructed which maps limited voltage data of the 8-electrode model to expanded voltage data of a quasi-16-electrode model. The predicted data is compared with the quasi-16-electrode data. Besides, image reconstruction based on L1 regularization method is conducted. Findings: The results show that the predicted data generally coincides with the quasi-16-electrode data. It is found that images reconstructed with the data of eight-electrode model are the poorest. Nevertheless, imaging results when the limited data is expanded by the proposed method show large improvement, and there is a minor difference with the images recovered with the quasi-16-electrode data. Also, the impact of noise is studied, which shows that the proposed method is robust to noise. Originality/value: To enhance reconstruction quality in the case of limited measurement, a new data expansion method based on the shallow convolutional neural network is proposed. Both simulation work and phantom experiments have demonstrated that high-quality images of cerebral hemorrhage and cerebral ischemia can be obtained when the limited measurement is expanded by the proposed method. [ABSTRACT FROM AUTHOR]

Background and Objectives: Early in the global COVID-19 pandemic, a concern was raised that potentially high volumes of COVID-19 inpatients in general hospitals might compromise the hospitals' capabilities to maintain high-quality care for routine patients and, thereby, to comply with indicators specifying quality of care. The objective of this study is to evaluate the impact of the surges of COVID-19 inpatients into general hospitals in Israel on the compliance rates for selected quality indicators reported by these hospitals within the Israeli National Program for Quality Indicators (NPQI). Methods: Compliance rate data were collected from the quality indicators reports made to the NPQI by participating hospitals. COVID-19 inpatient volume data were obtained from the Ministry of Health Digital Technologies and Data Division. Both datasets were analyzed on a week-by-week basis and plotted one alongside the other on a time scale. Association of each quality indicator's compliance rate with the number of COVID-19 inpatients was tested by Pearson's correlation analysis. The study included data from July 1, 2019 through June 30, 2022, spanning the duration of the COVID-19 pandemic in Israel. Five quality indicators included in the study were: Surgical repair of femoral neck fracture within 48 h of admission; Assessment of cerebral ischemic event risk for patients with atrial fibrillation; Duplex carotid ultrasound within 72 h of emergency department admission for patients with suspected transient ischemic attack; Antibiotic prophylaxis for caesarean sections ; and Percutaneous coronary intervention within 90 min for patients presenting with ST-elevation myocardial infarction. Results: Compliance rates for five quality indicators, representing different aspects of routine health care, remained steady – even at times with high volumes of COVID-19 inpatients in general hospitals. This lack of effect was prominent throughout the analyzed period, i.e., general hospitals maintained similar compliance rates for all quality indicators both during the surges of COVID-19 patients and between these periods. Statistical analysis showed no correlation between the quality indicators' compliance rates and the number of COVID-19 inpatients. Conclusions: Our findings indicate that high volumes of COVID-19 inpatients in general hospitals did not affect the hospitals' capability to comply with routine health care quality indicators. The results of our study imply that general hospitals in Israel were able to withstand the challenges associated with the care of COVID-19 inpatients while preserving high quality of care for routine patients. [ABSTRACT FROM AUTHOR]

The study of mitochondrial dysfunction has become increasingly pivotal in elucidating the pathophysiology of various cerebral pathologies, particularly neurodegenerative disorders. Mitochondria are essential for cellular energy metabolism, regulation of reactive oxygen species (ROS), calcium homeostasis, and the execution of apoptotic processes. Disruptions in mitochondrial function, driven by factors such as oxidative stress, excitotoxicity, and altered ion balance, lead to neuronal death and contribute to cognitive impairments in several brain diseases. Mitochondrial dysfunction can arise from genetic mutations, ischemic events, hypoxia, and other environmental factors. This article highlights the critical role of mitochondrial dysfunction in the progression of neurodegenerative diseases and discusses the need for targeted therapeutic strategies to attenuate cellular damage, restore mitochondrial function, and enhance neuroprotection. [ABSTRACT FROM AUTHOR]

Background Carotid artery intraluminal thrombus (ILT), or free- floating thrombus, is an uncommon cerebrovascular entity with considerable equipoise regarding its clinical management. Likewise, in patients treated with medical management (MM), distal embolization and/or intracranial hemorrhage (ICH) may still occur. Methods All patients with symptomatic ILT from 2016 to 2023 were identified from our tertiary care institution. Patients with MM failure (recurrent cerebral ischemia and/or symptomatic ICH) were compared with patients with MM non- failure. Differences in ILT volume and length were calculated. Receiver operator characteristic (ROC) curve analysis was used to identify the cut- off volume and length for risk of MM failure. Results In total, 45 patients with ILT were identified with 41 treated with frontline MM. Of these 41 patients treated with MM, seven (17%) had MM failure with six (14.6%) having new embolic stroke and one (2.3%) with symptomatic ICH. Patients with MM failure had a significantly higher mean thrombus volume than MM non- failure patients (257 mm³ vs 59.6 mm³, P=0.0006). Likewise, patients with MM failure had significantly longer thrombus on average (21 mm vs 6.6 mm, P=0.0009). ROC curve analysis showed that an ILT volume of 90 mm³ resulted in a sensitivity of 71.4% and specificity of 85.3% for MM failure (AUC 0.775; CI 0.55 to 1.0, P=0.023). Conclusions Carotid ILTs that fail MM are significantly larger and longer. These findings suggest that a thrombus volume of 90 mm3 may serve as a guide for intervention with good sensitivity and specificity for risk of MM failure. [ABSTRACT FROM AUTHOR]

Background Delayed cerebral ischemia (DCI) is one of the main contributors to poor clinical outcome after aneurysmal subarachnoid hemorrhage (SAH). Endovascular spasmolysis with intra-arterial nimodipine (IAN) may resolve angiographic vasospasm, but its effect on infarct prevention and clinical outcome is still unclear. We report the effect of IAN on infarction rates and functional outcome in a consecutive series of SAH patients. Methods To assess the effectiveness of IAN, we collected functional outcome data of all SAH patients referred to a single tertiary center since its availability (2011-2020). IAN was primarily reserved as a last tier option for DCI refractory to induced hypertension (iHTN). Functional outcome was assessed after 12 months according to the Glasgow Outcome Scale (GOS, favorable outcome = GOS4-5). Results Out of 376 consecutive SAH patients, 186 (49.5%) developed DCI. Thereof, a total of 96 (25.5%) patients remained unresponsive to iHTN and received IAN. DCI-related infarction was observed in 44 (45.8%) of IAN-treated patients with a median infarct volume of 111.6 mL (Q1: 51.6 to Q3: 245.7). Clinical outcome was available for 84 IAN-treated patients. Of those, a total of 40 (47.6%) patients reached a favorable outcome after 1 year. Interventional complications were observed in 9 (9.4%) of the IAN-treated patients. Conclusion Intra-arterial spasmolysis using nimodipine infusion was associated with low treatment specific complications. Despite presenting a subgroup of severely affected SAH patients, almost half of IAN-treated patients were able to lead an independent life after 1 year of follow-up. [ABSTRACT FROM AUTHOR]

Background Competitive leptomeningeal flow (CLF) can be observed immediately after mechanical thrombectomy (MT) reperfusion with retrograde contrast clearing of the distal leptomeningeal branches from non-contrast opacified flow through different vascular territories. We aim to evaluate the frequency of the CLF phenomenon, to determine if it has an association with the degree of leptomeningeal collateral status, and to understand the potentia impact it may have on the final expanded Treatment in Cerebral Ischemia (eTICI) score rating. Methods Retrospective analysis of a prospective MT database spanning November 2020 to December 2021. Consecutive cases of intracranial internal carotid (i-ICA) or middle cerebral artery (MCA) M1 occlusions were included. CLF was defined by the observation of retrograde clearing of distal MCA branches that were previously opacified by antegrade reperfusion. The clearance of the distal branches is presumed to occur due to CLF via non-contrast opacified posterior cerebral artery or anterior cerebral artery flow. The washout was considered CLF if it cleared abruptly with or without forward reconstitution of antegrade opacification. Results A total of 125 patients met the inclusion criteria. The median age was 64 years (IQR 52.5-75) and 64 (51%) were men. The baseline median National Institutes of Health Stroke Scale score was 17 (IQR 12-22) and the Alberta Stroke Program Early CT Score was 9 (IQR 8-10). Median last known well time to puncture was 7 hours (IQR 4-13.1) and 30.4% received tissue plasminogen activator. Final eTICI 2c-3 was achieved in 80%. CLF was present in 32 (25.6%) patients, who had comparable baseline characteristics to patients without CLF. Twelve (37.5%) patients had regional CLF and 20 (62.5%) had focal CLF. The CLF arm had better leptomeningeal single-phase CTA collaterals than the non-CLF arm (P=0.01). The inter-rater agreement for the eTICI score was moderate when CLF was present and strong in its absence (Krippendorf's alpha=0.65 and 0.81, respectively). There was minimal agreement (Kappa=0.3) for the presence versus absence of CLF between the two operators, possibly related to reader experience. Conclusion CLF was observed in 32% of patients, was associated with better collateral flow, and impacted the reported procedural eTICI rating. [ABSTRACT FROM AUTHOR]

Objective: To investigate the therapeutic effect of Xiangshao Granules (XSG) on post-stroke depression (PSD) and explore the underlying mechanisms. Methods: Forty-three C57BL/6J mice were divided into 3 groups: sham (n=15), PSD+vehicle (n=14), and PSD+XSG (n=14) groups according to a random number table. The PSD models were constructed using chronic unpredictable mild stress (CUMS) after middle cerebral artery occlusion (MCAO). The sham group only experienced the same surgical operation, but without MACO and CUMS stimulation. The XSG group received XSG (60 mg/kg per day) by gavage for 4 weeks. The mice in the sham and vehicle groups were given the same volume of 0.9% saline at the same time. The body weight and behavior tests including open field test, sucrose preference test, tail suspension test, and elevated plus-maze test, were used to validate the PSD mouse model. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining were used to evaluate the anti-inflammatory effects of XSG. The potential molecular mechanisms were explored and verified through network pharmacology analysis, Nissl staining, Western blot, ELISA, and RT-qPCR, respectively. Results: The body weight and behavior tests showed that MCAO combined with CUMS successfully established the PSD models. XSG alleviated neuronal damage, reduced the expressions of pro-apoptotic proteins Caspase-3 and B-cell lymphoma-2 (BCL-2)-associated X (BAX), and increased the expression of anti-apoptotic protein BCL-2 in PSD mice (P<0.05 or P<0.01). XSG inhibited microglial activation and the expressions of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1 β, and IL-6 via the toll-like receptor 4/nuclear factor kappa-B signaling pathway in PSD mice (P<0.05 or P<0.01). Furthermore, XSG decreased the expression of indoleamine 2,3-dioxygenase1 (IDO1) and increased the concentration of 5-hydroxytryptamine in PSD mice (P<0.05 or P<0.01). Conclusion: XSG could reverse the anxiety/depressionlike behaviors and reduce the neuronal injury in the hippocampus and prefrontal cortex of PSD mice, which may be a potential therapeutic agent for PSD. [ABSTRACT FROM AUTHOR]

Background: Stroke is a major neurological disorder often exacerbated by substance abuse, including tramadol and cannabis. Understanding the molecular mechanisms underlying stroke pathogenesis in drug users can improve diagnosis and treatment. This study explores the roles of CYP4A11, CYP2E1, miR-27b, and miR-214-3p in the pathogenesis of stroke and their potential as diagnostic markers in individuals using tramadol and cannabis. Results: Our findings indicate that CYP4A11 and CYP2E1 are significantly upregulated in the brain tissues of stroke patients who use tramadol and cannabis. Additionally, miR-27b and miR-214-3p levels were markedly altered, suggesting their involvement in stroke pathogenesis. The combined analysis of these biomarkers provided a robust diagnostic model with high sensitivity and specificity for identifying stroke in the context of drug addiction. Conclusions: CYP4A11, CYP2E1, miR-27b, and miR-214-3p play critical roles in the pathogenesis of stroke in tramadol and cannabis users. These biomarkers hold promise as diagnostic tools, offering potential for early detection and personalized treatment strategies for stroke in drug-addicted populations. Further research is warranted to validate these findings and explore their therapeutic implications. [ABSTRACT FROM AUTHOR]

Promoting vascular endothelial cell regeneration can enhance recovery from cerebral ischemia reperfusion injury (CIRI), but there is a lack of bioinformatic studies on angiogenesis-related biomarkers in CIRI. In this study, we utilized the GSE97537 and GSE61616 datasets from GEO to identify 181 angiogenesis-related genes (ARGs) and analyzed differentially expressed genes (DEGs) between CIRI and control groups. We converted ARGs to 169 rat homologues and intersected them with DEGs to find DE-ARGs. RF and XGBoost models were employed to identify five biomarkers (Stat3, Hmox1, Egfr, Col18a1, Ptgs2) and conducted GSEA on these biomarkers, revealing their enrichment in pathways such as ECM-receptor interaction and hematopoietic cell lineage. We also analyzed the immune microenvironment, finding significant differences in 21 immune cells between CIRI and control groups. Furthermore, we constructed lncRNA-miRNA-mRNA networks and drug-gene networks. Finally, biomarker expression was compared between the CIRI and control groups by qRT-PCR in tissue and blood samples. Overall, our bioinformatic exploration of angiogenesis-related biomarkers in CIRI provides new insights for the diagnosis and treatment of CIRI. [ABSTRACT FROM AUTHOR]