Treatment Of Ischemic Stroke Research Articles

Intravenous Thrombolysis with Urokinase for Acute Ischemic Stroke.

Intravenous thrombolysis is one of the most effective therapies for the treatment of acute ischemic stroke (AIS), with urokinase offering a cost-effective alternative to newer agents like alteplase and tenecteplase, especially in resource-limited settings. This review provides a comprehensive overview of the application of intravenous thrombolysis with urokinase for AIS in the clinical practice of stroke management, including the efficacy, safety, and cost-effectiveness of urokinase compared to other thrombolytic agents. Urokinase, a first-generation thrombolytic drug, is a non-specific plasminogen activator that offers a cost-effective alternative. It has been used in clinical practice for over two decades to improve neurological outcomes in patients with AIS if administered within 6 h of ictus. Numerous studies have indicated that urokinase remains a viable option for patients who cannot access alteplase or tenecteplase because of economic constraints, time window limitations, availability, or other reasons. In low- and middle-income countries, urokinase is a cost-effective alternative thrombolytic drug. High-level evidence-based medical research is therefore urgently needed to confirm that urokinase is not inferior to new-generation thrombolytic drugs, and to assess whether it may even be superior in some patient populations.

Cyclic Aspiration in Mechanical Thrombectomy: Influencing Factors and Experimental Validation.

Mechanical thrombectomy is a fundamental intervention for acute ischemic stroke treatment. While conventional techniques are effective, cyclic aspiration (CyA) shows potential for better recanalization rates. We aim to investigate factors affecting CyA and compare them with static aspiration (StA). StA setup consisted of an aspiration pump connected to pressure transducer. CyA was tested with 5 subsequent iterations: single solenoid valve with air plus saline (i1) or saline alone (i2) as aspiration medium; 2 solenoid valves with air plus saline (i3) as aspiration medium; complete air removal and saline feeding (i4); and pressurized saline feeding (i5). To assess the efficacy of clot ingestion, the pressure transducer was replaced with a distal aspiration catheter. Moderately stiff clot analogs (15 mm) were used to investigate the ingestion quantified as clot relative weight loss. Additionally, the aspiration flow rate was assessed for each setup. With CyA i1, the amplitude of the achieved negative pressure waves declined with increasing frequencies but progressively increased with each subsequent iteration, achieving a maximum amplitude of 81 kPa for i5 at 1 Hz. Relative clot weight loss was significantly higher with i5 at 5 Hz than with StA (100% versus 37.8%; P = .05). Aspiration flow rate was lower with CyA than with StA (i5 at 5 Hz: 199.8 mL/min versus StA: 311 mL/min; P < .01). CyA with the appropriate setup may represent an encouraging innovation in mechanical thrombectomy, offering a promising pathway for improving efficacy in clot ingestion and recanalization. The observed benefits warrant confirmation in a clinical setting.

Safety and effectiveness of SOFIA/SOFIA PLUS for direct aspiration as first line treatment in patients with acute anterior ischemic stroke: results from the prospective, multicentric SESAME study.

Mechanical thrombectomy is a cornerstone treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO), yet the optimal technique remains debated. The SOFIA/SOFIA PLUS catheter has emerged as a promising tool for direct aspiration thrombectomy. This prospective multi-center study, adhering Good-Clinical-Practice guidelines, aimed to evaluate the safety and efficacy of the SOFIA/SOFIA PLUS catheter for direct aspiration as a first-line treatment technique in patients with acute anterior circulation LVO. Between 10/2017 and 12/2021, 246 consecutive patients presenting with AIS due to anterior circulation LVO were enrolled from 14 European centers. Primary treatment with SOFIA catheters was performed within 6 h of symptom onset. Clinical and radiological data were collected, and statistical analyses were conducted. The mean age of the included patients was 71.6 ± 13.9 years, with 44.7% being male. Primary aspiration achieved complete recanalization in 72.8% of patients, with functional independence observed in 63.8% after 90 days. Secondary outcomes included a median NIHSS of 4 at 24 h post-procedure, median ASPECTS of 7 on follow-up imaging, and a mortality rate of 24.4% at 90 days. No device malfunctions were observed, and the rate of symptomatic intracranial hemorrhage was 4.4%. Primary aspiration with the SOFIA/SOFIA PLUS catheter demonstrates favorable safety and efficacy profiles in the treatment of anterior circulation LVO. These findings support the utilization of this technique as a first-line approach in mechanical thrombectomy for AIS, contributing to the growing body of evidence endorsing the effectiveness of direct aspiration thrombectomy in stroke management.

Streamlining Acute Stroke Processes and Data Collection: A Narrative Review

(1) Background: Acute ischemic stroke treatment has been thoroughly studied to identify strategies to reduce treatment times. However, many centers still struggle to achieve fast treatment times. Additionally, studies primarily focus on larger, more advanced centers; yet, smaller centers often face longer treatment times. (2) Objectives: The aim of this study is to analyze the existing literature reviewing stroke treatment processes in primary and comprehensive stroke centers that investigated or reduced treatment times. The articles identified were categorized based on the focus areas and approaches used. (3) Results: Three main categories of improvements were identified in the literature: (1) standardization of processes, (2) resource management, and (3) data collection. Both primary and comprehensive stroke centers were able to reduce treatment times through standardization of the processes. However, challenges such as variations in hospital resources and difficulties incorporating data collection software into workflow were highlighted. Additionally, many strategies to optimize resources and data collection that can benefit primary stroke centers were only conducted in comprehensive stroke centers. (4) Conclusions: Many existing strategies to improve stroke treatment times, such as pre-notification and mass stroke team alerts, have been implemented in both primary and comprehensive stroke centers. However, tools such as simulation training are understudied in primary stroke centers and should be analyzed. Additionally, while data collection and feedback are recognized as crucial for process improvement, challenges persist in integrating consistent data collection methods into clinical workflow. Further development of easy-to-use software tailored to clinician needs can help improve stroke center capabilities to provide feedback and improve treatment processes.

Causal relationship between novel antidiabetic drugs and ischemic stroke: a drug-targeted Mendelian randomization study.

The escalating global economic burden of ischemic stroke poses a significant public health challenge amid global aging trends. The broad therapeutic efficacy of new antidiabetic drugs may offer new options in the prevention and treatment of ischemic stroke. Consistent conclusions regarding the relationship between novel antidiabetic agents and the risk of ischemic stroke remain elusive, and the causal relationship deserves further investigation. Three novel antidiabetic drug targets were selected, and cis-expression quantitative trait loci (cis-eQTL) were screened as instrumental variables. Genetic association data for ischemic stroke were obtained from the Genome-wide Association Study (GWAS) database. Mendelian randomization (MR) analysis, facilitated by R software, calculated MR estimates for each single nucleotide polymorphism (SNP), and meta-analysis was performed using five methods. To ensure robustness, sensitivity analyses, heterogeneity analyses, horizontal pleiotropy analyses, and co-localization analyses were conducted for significant MR associations. Three eQTLs for antidiabetic drug genes served as instrumental variables, utilizing a GWAS dataset comprising 34,217 cases and 406,111 controls for ischemic stroke. Genetic variants in glucagon-like peptide-1 receptor agonists (GLP-1 RA) targets exhibited a positive correlation with ischemic stroke risk (OR 1.06, 95% CI 1.04-1.08, P = 0.000), while genetic variation in dipeptidyl peptidase 4 inhibitors (DPP-4i) targets showed a negative association with ischemic stroke risk (OR 0.93, 95% CI 0.89-0.97, P = 0.003). Sensitivity analyses supported robust conclusions, revealing no heterogeneity or horizontal pleiotropy. This study found that GLP-1 RA and DPP-4i were associated with an increased risk of ischemic stroke by MR analysis. Although sensitivity analyses provide support for this result, it contradicts previous knowledge. Therefore, the results of this study still need to treated with caution. Updated and more in-depth GWAS data and high-quality real-world data are expected to validate the results.

Exploring the role of traditional Chinese medicine rehabilitation in stroke based on microRNA-mediated pyroptosis: A review.

Stroke, also known as "cerebrovascular accident," is a disease caused by acute impairment of brain circulation, which has a high rate of disability and mortality. Ischemic stroke (IS) is the most common type of stroke and a major cause of death and disability worldwide. At present, there are still many limitations in the treatment of IS, so it may be urgent to explore more treatments for IS. In recent years, the clinical application of traditional Chinese medicine rehabilitation methods such as traditional Chinese medicine, acupuncture, massage, traditional exercises and modern rehabilitation technology has achieved good results in the treatment of IS. Concurrently, studies have identified microRNA (miRNA), which are intimately associated with traditional Chinese medicine rehabilitation, as regulators of pyroptosis through their influence on microglia activity, inflammatory response, oxidative stress, angiogenesis and other factors, but at present, the mechanism of this direction has not been systematically summarized. Consequently, this article delineates in detail the specific role of miRNA in IS and the related activation pathways of pyroptosis in IS. This article presents a detailed discussion of the role of microRNA-mediated pyroptosis in IS, with a particular focus on the signaling pathways involved. The aim is to provide new insights for the research of traditional Chinese medicine (TCM) rehabilitation in the prevention and treatment of IS. In addition, the article explores the potential of TCM rehabilitation in regulating miRNA-mediated pyroptosis to intervene in IS.

Baicalein Inhibits Cerebral Ischemia-Reperfusion Injury through SIRT6-Mediated FOXA2 Deacetylation to Promote SLC7A11 Expression.

Ischemic stroke (IS) poses a serious threat to patient survival. The inhibition of ferroptosis can effectively alleviate ischemia-reperfusion (I/R) injury, suggesting potential targets in the ferroptosis pathway for the treatment of IS. In this study, MCAO/R mice and OGD/R-induced HT22 cell were constructed. It was found that baicalein decreased ROS, MDA, and Fe2+ levels, upregulated GSH levels, and enhanced the expression of ferroptosis-related proteins (GPX4 and SLC7A11), downregulated the expression of proapoptotic proteins (Bax, cytochrome c, and cleaved caspase-3), and upregulated the expression of an antiapoptotic protein (Bcl-2), ameliorating cerebral I/R injury. In animal and cell models, Sirtuin6 (SIRT6) is downregulated, and Forkhead boxA2 (FOXA2) expression and acetylation levels are abnormally upregulated. SIRT6 inhibited FOXA2 expression and acetylation. Baicalein promoted FOXA2 deacetylation by upregulating SIRT6 expression. FOXA2 transcriptionally inhibits SLC7A11 expression. In conclusion, baicalein inhibited apoptosis and partially suppressed the role of ferroptosis to alleviate cerebral I/R injury via SIRT6-mediated FOXA2 deacetylation to promote SLC7A11 expression.

Specific mode electroacupuncture stimulation opens the blood-brain barrier of the infarcted border zone in rats during MCAO/R recovery via modulation of tight junction protein expression by VEGFA and NF-κB.

The blood-brain barrier (BBB) strictly limits the entry of most exogenous therapeutic drugs into the brain, which brings great challenges to the drug treatment of refractory central diseases, including the treatment of ischemic stroke. Our previous studies have shown that specific mode electroacupuncture stimulation (SMES) can temporarily open the BBB, but with the mechanisms largely unknown. This study explored whether SMES opens the BBB in the infarcted border zone of rats during middle cerebral artery occlusion/reperfusion recovery, and whether this is related to p65 or vascular endothelial growth factor A (VEGFA) modulation of tight junction protein expression through in vivo and in vitro studies. Evans blue, FITC-dextran, mouse-derived nerve growth factor (NGF), and transendothelial electrical resistance values were used to evaluate the permeability of the BBB. Additionally, microvascular endothelial cells and astrocytes were utilized for in vitro study. Immunofluorescence, immunohistochemistry, western blot, and ELISA were employed to assess related protein expression. SMES significantly increased vascular permeability for Evans blue and NGF in the infarcted border zone, and increased the expression of VEGFA by activating p-p65, thereby reducing the expression of tight junction proteins Occludin and ZO-1. Correspondingly, oxygen glucose deprivation/reoxygenation activated p-p65 in and induced VEGFA secretion from astrocytes in vitro. Their conditioned medium reduced the expression of Occludin in bEnd.3 cells and increased the permeability of FITC-dextran. The mechanism of SMES opening infarcted border zone BBB is partly related to its actions on p65, VEGFA, and tight junction proteins.

Impact of double stent retriever configuration on first-pass effect in stroke: a multicenter study

BackgroundEfficient recanalization of occluded cerebral arteries is crucial in the treatment of acute ischemic stroke. Double stent retrievers have shown the potential to enhance the rates of recanalization on the...

ИНТЕГРИРОВАННЫЙ ПОДХОД ПРИ ЛЕЧЕНИИ РАНЕНИЙ ШЕИ: ОТ ОТКРЫТОЙ ХИРУРГИИ ДО ЭНДОВАСКУЛЯРНЫХ ТЕХНОЛОГИЙ

Neck wounds are a serious problem in peacetime and wartime because of the high mortality and severity of the condition of the injured. This article presents a clinical observation of a patient with a gunshot wound of the neck, injury and occlusion of the common carotid artery. The wounded person underwent subclavian-carotid allografting, which was complicated by its thrombosis and subsequent middle cerebral artery embolism. The authors describe the efficacy of multidisciplinary management of this case, including surgery and endovascular treatment. The results indicate the efficacy of surgical treatment for common carotid artery occlusions, but emphasize the possibility of unforeseen complications. An approach involving detection of ischemic stroke and endovascular treatment, including thrombaspiration and intra-arterial thrombolysis, can prevent serious complications in patients with such lesions.

Ferroptosis in Ischemic Stroke and Related Traditional Chinese Medicines.

Stroke is a severe neurological disorder resulting from the rupture or blockage of blood vessels, leading to significant mortality and disability worldwide. Among the different types of stroke, ischemic stroke (IS) is the most prevalent, accounting for 70-80% of cases. Cell death following IS occurs through various mechanisms, including apoptosis, necrosis, and ferroptosis. Ferroptosis, a recently identified form of regulated cell death characterized by iron overload and lipid peroxidation, was first described by Dixon in 2012. Currently, the only approved pharmacological treatment for IS is recombinant tissue plasminogen activator (rt-PA), which is limited by a narrow therapeutic window and often results in suboptimal outcomes. Recent research has identified several traditional Chinese medicines (TCMs) that can inhibit ferroptosis, thereby mitigating the damage caused by IS. This review provides an overview of stroke, the role of ferroptosis in IS, and the potential of certain TCMs to inhibit ferroptosis and contribute to stroke treatment.

In vitro assessment of vascular injury following stent retriever retraction in clinically-relevant endothelialized silicone models.

Mechanical thrombectomy devices have potential to injure the vessel during treatment of acute ischemic stroke. The goal of the current work was to tailor in vitro endothelialized silicone models for stent retriever assessment and to evaluate endothelial injury following treatment by various stent retriever designs and sizes. Clinically-relevant neurovascular geometries were first modeled out of silicone, then sterilized, coated with fibronectin, placed in bioreactors, seeded with human endothelial cells, and cultivated under flow. Several sizes of two different commercially available stent retrievers were then deployed in, and retracted through, vessels. Vessels were immediately harvested and stained. Endothelial injury, identified as denudation, was quantified using ImageJ. Results illustrated that endothelial injury ranged from 16-18% in wire/microcatheter-only treated vessels, 37-61% in 1-pass treatments, and 52-70% in 2-pass treatments. Overall this work showcases an in vitro approach for early stage assessment of the extent and location of vascular injury following stent retriever retraction.

Mitofusin 2 Mediates the Protective Effect of NR6A1 Silencing Against Neuronal Injury in Experimental Stroke Models.

An abnormal increase in the expression of nuclear receptor subfamily 6 group A member 1 (NR6A1) in the hippocampus has been reported to result in depressive-like behavior in mice. However, the role of NR6A1 in the progression of neuronal death induced by ischemic stroke remains unknown. In this study, we observed an increase in NR6A1 in neurons in both in vivo and in vitro cerebral ischemic models. We found that knocking down NR6A1 in HT-22 neuronal cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) attenuated mitochondrial dysfunction and endoplasmic reticulum (ER) stress. Conversely, NR6A1 overexpression exacerbated neuronal damage following OGD/R. NR6A1 hindered the transcription of mitonfusin 2 (MFN2), leading to a decrease in its expression. In contrast, MFN2 conferred the protective effect of NR6A1 silencing against both mitochondrial dysfunction and ER stress. In addition, NR6A1 silencing also attenuated brain infarction, ER stress, neuronal apoptosis, and loss of MFN2 in mice subjected to middle cerebral artery occlusion/reperfusion. These findings indicate that NR6A1 is a promising target for the treatment of neuronal death following cerebral ischemia. Furthermore, these results confirm the involvement of MFN2 in the effects of NR6A1 silencing. Therefore, targeting NR6A1 has potential as a viable strategy for the treatment of ischemic stroke.

Qualitative Evaluation of a Quality Improvement Collaborative Implementation to Improve Acute Ischemic Stroke Treatment in Nova Scotia, Canada.

The Atlantic Canada Together Enhancing Acute Stroke Treatment (ACTEAST) project is a modified quality improvement collaborative (mQIC) designed to improve ischemic stroke treatment rates and efficiency in Atlantic Canada. This study evaluated the implementation of the mQIC in Nova Scotia using qualitative methods. The mQIC spanned 6 months, including two learning sessions, webinars, and a per-site virtual visit. The learning sessions featured presentations about the project and the improvement efforts at some sites. Each session included an action planning period where the participants planned for the implementation efforts over the following 2 to 4 months, called "action periods". Eleven hospitals and Emergency Health Services (EHS) of Nova Scotia participated. The Consolidated Framework for Implementation Research (CFIR) was utilized to develop a semi-structured interview guide to uncover barriers and facilitators to mQIC's implementation. Interviews were conducted with 14 healthcare professionals from 10 entities, generating 458 references coded into 28 CFIR constructs. The interviews started on 17 June 2021, 2 months after the intervention period, and ended on 7 October 2021. Notably, 84% of these references were positively framed as facilitators., highlighting the various aspects of the mQIC and its context that supported successful implementation. These facilitators encompassed factors such as networks and communications, strong leadership engagement, and a collaborative culture. Significant barriers included resource availability, relative priorities, communication challenges, and engaging key stakeholders. Some barriers were prominent during specific phases. The study provides insights into quality improvement initiatives in stroke care, reflecting the generally positive opinions of the interviewees regarding the mQIC. While the quantitative analysis is still ongoing, this study highlights the importance of addressing context-specific barriers and leveraging the identified facilitators for successful implementation.

Deep Learning-Based ASPECTS Algorithm Enhances Reader Performance and Reduces Interpretation Time.

ASPECTS is a long-standing and well documented selection criteria for acute ischemic stroke treatment, however, the interpretation of ASPECTS is a challenging and time-consuming task for physicians with significant interobserver variabilities. We conducted a multi-reader, multi-case study in which readers assessed ASPECTS without and with the support of a deep learning (DL)-based algorithm in order to analyze the impact of the software on clinicians' performance and interpretation time. A total of 200 NCCT scans from 5 clinical sites (27 scanner models, 4 different vendors) were retrospectively collected. Reference standard was established through the consensus of three expert neuroradiologists who had access to baseline CTA and CTP data. Subsequently, eight additional clinicians (four typical ASPECTS reader and four senior neuroradiologists) analyzed the NCCT scans without and with the assistance of CINA-ASPECTS (Avicenna.AI, La Ciotat, France), a DLbased FDA-cleared and CE-marked algorithm designed to automatically compute ASPECTS. Differences were evaluated in both performance and interpretation time between the assisted and unassisted assessments. With software aid, readers demonstrated increased region-based accuracy from 72.4% to 76.5% (p<0.05), and increased ROC AUC from 0.749 to 0.788 (p<0.05). Notably, all readers exhibited an improved ROC AUC when utilizing the software. Moreover, use of the algorithm improved the score-based inter-observer reliability and correlation coefficient of ASPECTS evaluation by 0.222 and 0.087 (p<0.0001), respectively. Additionally, the readers' mean time spent analyzing a case was significantly reduced by 6% (p<0.05) when aided by the algorithm. With the assistance of the algorithm, readers' analyses were not only more accurate but also faster. Additionally, the overall ASPECTS evaluation exhibited greater consistency, less variabilities and higher precision compared to the reference standard. This novel tool has the potential to enhance patient selection for appropriate treatment by enabling physicians to deliver accurate and timely diagnosis of acute ischemic stroke. ASPECTS = Alberta Stroke Program Early Computed Tomography Score; DL = Deep Learning; EIC = Early Ischemic Changes; ICC = Intraclass Correlation Coefficient; IS = Ischemic Stroke; ROC AUC = Receiver Operating Characteristics Area Under the Curve.

Iatrogenic arterial vasospasm during mechanical thrombectomy requiring treatment with intra-arterial nimodipine might be associated with worse outcomes.

Vasospasm is a common iatrogenic event during mechanical thrombectomy (MT). In such circumstances, intra-arterial nimodipine administration is occasionally considered. However, its use in the treatment of iatrogenic vasospasm during MT has been poorly studied. We investigated the impact of iatrogenic vasospasm treated with intra-arterial nimodipine on outcomes after MT for large vessel occlusion stroke. We conducted a retrospective analysis of the multicenter observational registry Endovascular Treatment in Ischemic Stroke (ETIS). Consecutive patients treated with MT between January 2015 and December 2022 were included. Patients treated with medical treatment alone, without MT, were excluded. We also excluded patients who received another insitu vasodilator molecule during the procedure. Outcomes were compared according to the occurrence of cervical and/or intracranial arterial vasospasm requiring intraoperative use of insitu nimodipine based on operator's decision, using a propensity score approach. The primary outcome was a modified Rankin Scale (mRS) score of 0-2 at 90 days. Secondary outcomes included excellent outcome (mRS score 0-1), final recanalization, mortality, intracranial hemorrhage and procedural complications. Secondary analyses were performed according to the vasospasm location (intracranial or cervical). Among 13,678 patients in the registry during the study period, 434 received intra-arterial nimodipine for the treatment of MT-related vasospasm. In the main analysis, comparable odds of favorable outcome were observed, whereas excellent outcome was significantly less frequent in the group with vasospasm requiring nimodipine (adjusted odds ratio [aOR] 0.78, 95% confidence interval [CI] 0.63-0.97). Perfect recanalization, defined as a final modified Thrombolysis In Cerebral Infarction score of 3 (aOR 0.63, 95% CI 0.42-0.93), was also rarer in the vasospasm group. Intracranial vasospasm treated with nimodipine was significantly associated with worse clinical outcome (aOR 0.64, 95% CI 0.45-0.92), in contrast to the cervical location (aOR 1.37, 95% CI 0.54-3.08). Arterial vasospasm occurring during the MT procedure and requiring intra-arterial nimodipine administration was associated with worse outcomes, especially in case of intracranial vasospasm. Although this study cannot formally differentiate whether the negative consequences were due to the vasospasm itself, or nimodipine administration or both, there might be an important signal toward a substantial clinical impact of iatrogenic vasospasm during MT.

Combining systems pharmacology, metabolomics, and transcriptomics to reveal the mechanism of Salvia miltiorrhiza-Cortex moutan herb pair for the treatment of ischemic stroke.

Ischemic stroke (IS), predominantly triggered by blockages in cerebral blood flow, is increasingly recognized as a critical public health issue. The combination of Salvia miltiorrhiza (SM) and Cortex moutan (CM), traditional herbs in Eastern medicine, are frequently used for managing heart and brain vascular conditions. However, the exact mechanisms by which this herb pair (SC) combats IS remain largely unexplored. This investigation focuses on pinpointing the active constituents in SC that contribute to its protective role and deciphering the mechanisms countering cerebral ischemia, particularly in a middle cerebral artery occlusion (MCAO) rat model. We employed UPLC-Q-TOF-MS/MS alongside network pharmacology for predicting SC's target actions against IS. Key ingredients were examined for their interaction with principal targets using molecular docking. The therapeutic impact was gauged through H&E, TUNEL, and Nissl staining, complemented by transcriptomic and metabolomic integration for mechanistic insights, with vital genes confirmed via western blot. UPLC-Q-TOF-MS/MS analysis revealed that the main components of SC included benzoylpaeoniflorin, salvianolic acid B, oxypaeoniflora, salvianolic acid A, and others. Network pharmacology analysis indicated that SC's mechanism in treating IS primarily involves inflammation, angiogenesis, and cell apoptosis-related pathways, potentially through targets such as AKT1, TNF, PTGS2, MMP9, PIK3CA, and VEGFA. Molecular docking underscored strong affinities between these constituents and their targets. Our empirical studies indicated SC's significant role in enhancing neuroprotection in IS, with transcriptomics suggesting the involvement of the VEGFA/PI3K/AKT pathway and metabolomics revealing improvements in various metabolic processes, including amino acids, glycerophospholipids, sphingomyelin, and fatty acids metabolisms.

Human neural stem cell-derived extracellular vesicles protect against ischemic stroke by activating the PI3K/AKT/mTOR pathway.

Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells, and can thus be used as substitutes for stem cells in stem cell therapy, thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived treatments. This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke. However, the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear, presenting challenges for clinical translation. To promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside, we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic stroke. We found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis. The human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase, mammalian target of rapamycin, and protein kinase B, and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor. These findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. Finally, we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety profile. Therefore, human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.

A meta-analysis of the efficacy of Buyang Huanwu decoction in the treatment of ischemic stroke

A meta-analysis of the efficacy of Buyang Huanwu decoction in the treatment of ischemic stroke

Therapeutic Effects of Coenzyme Q10 in the Treatment of Ischemic Stroke.

Ischemic stroke is the second deadly disease worldwide, but current treatment is very limited. The brain, rich in lipids and high in oxygen consumption, is susceptible to damage from oxidative stress after ischemic stroke. Thus, antioxidants are promising neuroprotective agents for treatment and prevention of ischemic stroke. Coenzyme Q10 is the only lipophilic antioxidant that can be synthesized de novo by cells and plays a key role as an electron carrier in the oxidative phosphorylation of the mitochondrial electron transport chain. However, the reduced form of coenzyme Q10 (Ubiquinol) levels are significantly deficient in the brain. The aim of this article is to review the therapeutic effects and mechanisms of coenzyme Q10 in ischemic stroke. Current studies have found that coenzyme Q10 protects and treats ischemic stroke through multiple mechanisms based on the evidence from in vitro experiments, in vivo experiments, and clinical observations. For the first time, we reviewed the neuroprotective effects of coenzyme Q10 in ischemic stroke. Coenzyme Q10 exerts neuroprotective effects after ischemic stroke through anti-oxidative stress, anti-nitrosative stress, anti-inflammation, and anti-cell death. Here, we provided the evidence on the therapeutic and preventive effects of coenzyme Q10 in ischemic stroke and suggested the potential value of coenzyme Q10 as a medication candidate.