Treatment Of Ischemic Stroke Research Articles

A multicenter trial on the predictors of different subtypes of hemorrhagic infarction after thrombolysis

Worldwide, stroke is a leading cause of long-term disability in adults. Alteplase is the only approved treatment for acute ischemic stroke (AIS) and results in an improvement in a third of treated patients. Most studies evaluated the post-alteplase haemorrhagic transformation of brain infarction as a homogeneous entity but we evaluated the predictors of each subtype of haemorrhagic transformation of brain infarction. Our trial included 616 AIS alteplase-treated patients. We evaluated the ability of different risk factors, clinical presentation, and imaging features to predict different haemorrhagic transformation (HT) subtypes. HT was seen in 152 patients (24.7%), higher NIHSS, cardioembolic stroke and atrial fibrillation were independent predictors of all ECASS-based subtypes of hemorrhagic infarction, in addition, anterior-circulation stroke was an independent predictor of hemorrhagic infarction type 1 (odds ratio [OR], 11.04; 95% CI, 9.81 to 12.70; P-value > 0.001) and type2 (OR, 11.89; 95% CI, 9.79 to 14.44; P-value > 0.001), while older age was also an independent predictor of parenchymal hematoma type1 (OR, 1.312; 95% CI, 1.245 to 1.912; P-value 0.02). In AIS patients treated with alteplase in Egypt and Saudi Arabia, higher NIHSS, cardioembolic stroke and atrial fibrillation were independent predictors of all ECASS-based subtypes of hemorrhagic infarction; in addition, anterior-circulation stroke was an independent predictor of hemorrhagic infarction type 1 and 2, while older age was also an independent predictor of parenchymal hematoma type1. Trial registration: (clinicaltrials.gov NCT06337175), retrospectively registered on 29/03/2024.

Safety of alteplase intravenous thrombolysis and influencing factors of clinical outcome in elderly patients with acute ischemic stroke

ObjectiveTo explore the safety of intravenous thrombolysis with alteplase (rt-PA) in the treatment of acute ischemic stroke (AIS) in the elderly (≥ 80 years old) and with analyze the influencing factors of its clinical outcome.MethodsA total of 144 elderly patients (≥ 80 years old) with AIS who were admitted to our hospital from April 2018 to October 2019 were divided into the elderly thrombolytic group (n = 55) and the elderly non-thrombolytic group (n = 89) according to their different treatment methods, and 166 non-elderly AIS thrombolytic patients in the same period were selected as the non-elderly thrombolytic group. Routine antiplatelet therapy or anticoagulant therapy was given to the elderly non-thrombolytic group, while intravenous thrombolysis with rt-PA was given to the elderly thrombolytic group and the non-elderly thrombolytic group. The changes in National Institutes of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), and intracranial hemorrhage transformation within 7 days, mortality within 3 months were used to evaluate the prognosis and safety of patients in each group. Binary Logistic regression was used to analyze the independent factors affecting the long-term prognosis of thrombolytic therapy for AIS in the elderly.ResultsAfter the treatment, the short-term prognosis and the long-term prognosis improvement rates in the non-elderly thrombolytic group and the elderly thrombolytic group were higher than that in the elderly non-thrombolytic group (P < 0.05). There was no statistical difference in mortality between the elderly thrombolytic group and the elderly non-thrombolytic group or in intracranial hemorrhage transformation among the different groups (P > 0.05). Binary logistic regression analysis showed that NIHSS score before treatment was an independent risk factor affecting the long-term prognosis of elderly AIS patients after thrombolysis (P < 0.05).ConclusionElderly AIS patients after rt-PA thrombolysis therapy can improve the short-term, long-term prognosis. The risk of intracranial hemorrhage transformation and death is not higher than that of elderly non thrombolytic patients, indicating that rt-PA treatment is safe for elderly AIS patients. The NIHSS score before treatment was an independent risk factor affecting the long-term prognosis of elderly AIS patients after thrombolytic therapy.

Prehospital telemedicine support for urban stroke care: Analysis of current state of care and conceptualization

BackgroundThe reduction of processing times in the treatment of acute ischemic stroke is of outstanding importance. Our objective is to analyze the acute stroke care chain from onset to treatment in a city in Germany comprising three stroke units. Additionally, we discuss solutions for detected treatment delays.MethodsWe conducted an in-depth analysis of acute stroke care processing times across three local stroke centers in Düsseldorf among all emergency services transportations for suspected stroke. Isochrone mapping was performed to identify areas with prolonged transportation times.ResultsAmong the 1,714 transportations, 943 patients had confirmed strokes. Prehospital care constituted 58% of total emergency care time until imaging. Patients with confirmed stroke had reduced in-hospital times while patients receiving treatment experienced faster in-hospital times. Isochrone mapping revealed disparities in transportation times within the city.ConclusionsIn conclusion, we identified confirmation of stroke symptoms as pre- and in-hospital and treatment eligibility as in-hospital process accelerators in stroke care. We propose the introduction of an in-ambulance video consulting model to accelerate contact to stroke-experts and accelerate processing times for patients eligible for treatment. Furthermore, we discuss the combination of in-ambulance video consulting with imaging and starting treatment outside traditional stroke centers, followed by transportation to a stroke center during thrombolysis, which might further accelerate treatment in specific cases.

Critical Insights on Truthfully Reporting "Success Rates" in Modern Stroke Research: A Cautionary Tale.

In 2015, several trials confirmed the safety and efficacy of mechanical thrombectomy for acute ischemic stroke. These findings revolutionized acute ischemic stroke treatment and established mechanical thrombectomy as a standard of care. Subsequent studies have further validated that optimal clinical outcomes are closely associated with achieving higher grades of complete reperfusion and minimizing the number of retrieval attempts. As a result, in recent years, the field has seen a growing trend of publications aggressively pursuing the highest rates of angiographic success. This trend is further exacerbated by the proliferation of impressive individual case reports shared on social media platforms, often devoid of significant scientific merit or educational value. We aim to review the potential biases in authors, which may incur when reporting recanalization rates, and underscore the importance of truthfully reporting success rates.

An injectable extracellular matrix-mimicking conductive hydrogel for sequential treatment of ischemic stroke

Ischemic stroke (IS), the primary health and life threat, frequently results in significant neurological impairment. Current research on IS treatment concentrates mainly on modulating the inflammatory microenvironment, often overlooking the significance of electric fields in brain tissue regeneration. Developing microenvironment-responsive conductive hydrogel strategies for IS treatment presents a considerable challenge. Achieving a balance between ensuring hydrogel stability for sustained conductivity and a swift response to inflammation is a complex tradeoff. In this work, we innovatively grafted polyaniline-aminobenzenesulfonic acid-aminophenyl boronic acid onto gelatin (GM), which allows GM to engage in cross-linking reactions, forming a stable, multi-conductive hydrogel network. To enhance microenvironmental regulation and sequential treatment, pluronic F-127 grafted with lipoic acid was used to encapsulate aniracetam into PSA NPs, which were then embedded into the HA/GM/PSA hydrogel. Within the inflammatory microenvironment, boronate bonds break, releasing PSA NPs that reshape the environment while the hydrogel maintains its conductivity. Physical and electrochemical characterizations of the hydrogels revealed that they closely match the modulus (1–1.3 kPa) and conductivity (0.93 mS/cm) of brain tissue. Moreover, both in vitro and in vivo studies demonstrated that the hydrogels provide excellent antioxidant effects, anti-inflammatory functions, promote vascular regeneration, and mitigate neuronal apoptosis. Collectively, this strategy advances brain tissue repair following IS by synergistically enhancing long-term conductivity and rapid microenvironment remodeling.

Biomimetic Nanomotors for Deep Ischemia Penetration and Ferroptosis Inhibition in Neuroprotective Therapy of Ischemic Stroke.

Nerve injury represents the primary reason of mortality and disability in ischemic stroke, but effective drug delivery to the region of cerebral ischemia and hypoxia poses a significant challenge in neuroprotective treatment. To address these clinical challenges, a biomimetic nanomotor, Pt@LF is designed, to facilitate deep delivery of neuroprotective agents and inhibit ferroptosis in ischemic stroke. Pt@LF traverses the blood-brain barrier (BBB) and penetrates into deep cerebral ischemic-hypoxic areas due to the active targeting capacity of apo-lactoferrin (Apo-LF) and the self-propelling motion properties of nanomotors. Subsequently, Pt@LF loosens thrombus and alleviates the "no reflow" phenomenon via mechanical thrombolysis. Thanks to the various enzyme-like abilities and multi-target ferroptosis inhibition capability, Pt@LF ameliorates the inflammatory microenvironment and rescues dying neurons. In conclusion, Pt@LF demonstrates efficiently deep penetration and neuroprotective effects in vitro and vivo. And this study provides a promising therapeutic platform for the treatment of ischemic stroke.

Trends in utilization and impact of hospital procedural volume on mortality after endovascular thrombectomy for acute ischemic stroke

ObjectivesEndovascular thrombectomy (EVT) has become an established treatment for eligible acute ischemic stroke (AIS) patients, but data on mortality trends and the association between procedural volume and outcomes in the United States is limited. Materials and MethodsThis retrospective study analyzed data from the Nationwide Readmissions Database (NRD) to investigate trends in EVT utilization, outcomes, and the relationship between hospital procedural volume and inpatient mortality for AIS admissions between 2016-2020. Patients undergoing EVT were identified using ICD-10 procedure codes. Hospitals were categorized into quintiles based on EVT volumes, and mortality rates compared across quintiles. Multivariable regression identified predictors of mortality. ResultsOf 2,535,777 AIS admissions, 90,110 (3.6 %) underwent EVT (median age of 70 and 50 % female in both groups). EVT utilization increased from 2.8 % in 2016 to 3.9 % in 2020 (p < 0.001). Patients receiving EVT had higher prevalence of atrial fibrillation and coronary artery disease but lower rates of hyperlipidemia and tobacco use. Inpatient mortality was higher with EVT (13 % vs 4 %, p < 0.001) but declined from 16 % in 2016-2017 to 12 % in 2020 (p < 0.001). Hemiparalysis and atrial fibrillation were associated with higher EVT likelihood. Mortality decreased with higher hospital EVT volume. After adjustment, higher procedural centers were associated with lower mortality. ConclusionEVT utilization for AIS increased nationally from 2016-2020 while associated mortality declined. Higher hospital procedural volumes were associated with lower mortality.

Exploring therapeutical targets and innovative treatments for ischemic stroke: a comprehensive review

This review focuses on the current advances in the field of therapeutic targets and treatments for stroke. Stroke is a major health problem worldwide, with significant impacts on morbidity and mortality, and a considerable burden on the medical and socio-economic systems. This review provides a comprehensive overview of the current state of knowledge on acute treatments and therapeutic targets. Current stroke treatments like recanalization therapies focus mainly on restoring blood flow to the brain, reducing cell death, and preventing further damage, but have limitations in terms of efficacy and long-term outcomes. Besides acute treatments (mobile stroke units, telerehabilitation) and acute therapeutic targets, the review focuses on longer-term therapeutic targets, such as neuroprotection and neuroregeneration. Neuroprotective strategies target the mechanisms underlying energy failure, cellular acidosis, mitochondrial dysfunction, endoplasmic reticulum stress, excitotoxicity, calcium channels dysregulation, oxidative stress, neuroinflammation, blood-brain barrier disruption, apoptosis, and ischemia-reperfusion injury. Neuroregenerative approaches include stem cell therapy, gene therapy, growth factors, and rehabilitation techniques that promote the rewiring of neuronal circuits in the brain. Non-pharmacological treatments like neurostimulation and bioengineering are also presented. Additionally, we highlight the challenges and future directions in translating these therapies into clinical practice. Overall, the treatment of ischemic stroke is a complex and multifaceted process that requires a combination of acute measures as well as longer-term strategies to promote brain repair and recovery. The treatment of ischemic stroke has made significant progress in recent years with the development of new treatments and ongoing research to improve outcomes for stroke patients. However, before these therapies can be successfully integrated into routine clinical practise, further research is needed to establish standardised protocols, overcome methodological limitations, and overcome clinical challenges. By further deepening our understanding of the pathophysiology of ischemic stroke and developing innovative treatments, we can improve outcomes and quality of life for stroke survivors.

Prevalence of ipsilateral “vulnerable carotid plaques with

BackgroundCarotid plaques may be an important etiology in ischemic stroke. We aimed to assess carotid plaque characteristics ipsilateral and contralateral to the ischemic stroke and assessed the prevalence of “vulnerable carotid plaques with <50% stenosis” based on different imaging-based definitions in patients with large vessel occlusion and source of embolic stroke of undetermined source (ESUS) on CT Angiography (CTA). MethodsData are from the ESCAPE-NA1 trial (Efficacy and safety of nerinetide for the treatment of acute ischemic stroke), a multicenter, randomized study that included anterior circulation large vessel occlusion patients undergoing thrombectomy. Various CTA features of plaque vulnerability were combined to define “vulnerable carotid plaques” in different ways. Within ESUS patients, prevalence of vulnerable plaques ipsilateral vs. contralateral to the intracranial occlusion was compared. ResultsWe analyzed 132 patients whose ischemic stroke mechanism was determined to be ESUS. Plaques causing 30–50 % stenosis (as compared to no stenosis) and plaque surface irregularity were significantly more common in ipsilateral carotid arteries (37[28.0 %] vs. 18[13.6 %]; p < 0.001 and 102[77.3 %] vs. 78[59.1 %]; p = 0.002). The prevalence of ipsilateral “vulnerable carotid plaques” varied depending on imaging definition used for such plaques between 55 and 74 %, but irrespective of the definition used, the prevalence of “vulnerable carotid plaques” was consistently higher in ipsilateral carotid arteries compared to contralateral carotid arteries. ConclusionsIn ESUS patients undergoing thrombectomy for anterior circulation large vessel occlusion, vulnerable carotid plaques are more prevalent ipsilateral to the intracranial occlusion. Irregular plaque surface, and a higher degree of stenosis were the most common vulnerable plaque features.

GIV/Girdin Modulation of Microglial Activation in Ischemic Stroke: Impact of FTO-Mediated m6A Modification.

Ischemic stroke (IS) is one of the most common causes of death in the world. The lack of effective pharmacological treatments for IS was primarily due to a lack of understanding of its pathogenesis. Gα-Interacting vesicle-associated protein (GIV/Girdin) is a multi-modular signal transducer and guanine nucleotide exchange factor that controls important signaling downstream of multiple receptors. The purpose of this study was to investigate the role of GIV in IS. In the present study, we found that GIV is highly expressed in the central nervous system (CNS). GIV protein level was decreased, while GIV transcript level was increased in the middle cerebral artery occlusion reperfusion (MCAO/R) mice model. Additionally, GIV was insensitive lipopolysaccharide (LPS) exposure. Interestingly, we found that GIV overexpression dramatically restrained microglial activation, inflammatory response, and M1 polarization in BV-2 microglia induced by oxygen-glucose deprivation and reoxygenation (OGD/R). On the contrary, GIV knockdown had the opposite impact. Mechanistically, we found that GIV activated the Wnt/β-catenin signaling pathway by interacting with DVL2 (disheveled segment polarity protein 2). Notably, m6A demethylase fat mass and obesity-associated protein (FTO) decreased the N6-methyladenosine (m6A) modification-mediated increase of GIV expression and attenuated the inflammatory response in BV-2 stimulated by OGD/R. Taken together, our results demonstrate that GIV inhibited the inflammatory response via activating the Wnt/β-catenin signaling pathway which expression regulated in an FTO-mediated m6A modification in IS. These results broaden our understanding of the role of the FTO-GIV axis in IS development.

A direct aspiration first-pass technique (ADAPT) for acute ischemic stroke thrombectomy: Indications, technique, and emerging devices.

To date, the use of the most suitable first-pass technique for Mechanical Thrombectomy is still debated. In last years, several observational studies have suggested noninferiority or superiority of A Direct Aspiration first-Pass Technique (ADAPT) technique to achieve better reperfusion in comparison to stent retriever. While ASA/AHA 2018 guidelines recommend that patients with AIS should receive Mechanical Thrombectomy with a stent retriever, last European Stroke Organization guidelines report no evidence that stent retriever compared with contact aspiration could improve reperfusion rate. ADAPT is based on aspiration alone as the primary mechanism of thrombectomy and, if initially unsuccessful, then incorporating adjunctive alternatives. ADAPT improvement is also related to last generation of aspiration catheters. The purpose of this review is to report ADAPT principles, technique, efficacy, and safety as first-line treatment for acute ischemic stroke with the latest generation of reperfusion devices.

Gut Microbe-Generated Metabolite Trimethylamine-N-Oxide and Ischemic Stroke.

Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite, the production of which in vivo is mainly regulated by dietary choices, gut microbiota, and the hepatic enzyme flavin monooxygenase (FMO), while its elimination occurs via the kidneys. The TMAO level is positively correlated with the risk of developing cardiovascular diseases. Recent studies have found that TMAO plays an important role in the development of ischemic stroke. In this review, we describe the relationship between TMAO and ischemic stroke risk factors (hypertension, diabetes, atrial fibrillation, atherosclerosis, thrombosis, etc.), disease risk, severity, prognostic outcomes, and recurrence and discuss the possible mechanisms by which they interact. Importantly, TMAO induces atherosclerosis and thrombosis through lipid metabolism, foam cell formation, endothelial dysfunction (via inflammation, oxidative stress, and pyroptosis), enhanced platelet hyper-reactivity, and the upregulation and activation of vascular endothelial tissue factors. Although the pathogenic mechanisms underlying TMAO's aggravation of disease severity and its effects on post-stroke neurological recovery and recurrence risk remain unclear, they may involve inflammation, astrocyte function, and pro-inflammatory monocytes. In addition, this paper provides a summary and evaluation of relevant preclinical and clinical studies on interventions regarding the gut-microbiota-dependent TMAO level to provide evidence for the prevention and treatment of ischemic stroke through the gut microbe-TMAO pathway.

Gut Microbiota and Tryptophan Metabolism in Pathogenesis of Ischemic Stroke: A Potential Role for Food Homologous Plants.

The intestinal flora is involved in the maintenance of human health and the development of diseases, and is closely related to the brain. As an essential amino acid, tryptophan (TRP) participates in a variety of physiological functions in the body and affects the growth and health of the human body. TRP catabolites produced by the gut microbiota are important signaling molecules for microbial communities and host-microbe interactions, and play an important role in maintaining health and disease pathogenesis. The review first demonstrates the evidence of TRP metabolism in stroke and the relationship between gut microbiota and TRP metabolism. Furthermore, the review reveals that food homologous plants (FHP) bioactive compounds have been shown to regulate various metabolic pathways of the gut microbiota, including the biosynthesis of valine, leucine, isoleucine, and vitamin B6 metabolism. The most notable metabolic alteration is in TRP metabolism. The interaction between gut microbiota and TRP metabolism offers a plausible explanation for the notable bioactivities of FHP in the treatment of ischemic stroke (IS). This review enhances the comprehension of the underlying mechanisms associated with the bioactivity of FHP on IS.

Preclinical safety and efficacy evaluation of the intrathecal transplantation of GMP-grade human umbilical cord mesenchymal stem cells for ischemic stroke.

Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke, but its safety, effectiveness, and mechanism remain to be elucidated. In this study, good manufacturing practice-grade human umbilical cord mesenchymal stem cells (5 × 105 and 1 × 106 cells) and saline were administered by cerebellomedullary cistern injection 72 hours after stroke induced by middle cerebral artery occlusion in rats. The results showed (1) no significant difference in mortality or general conditions among the three groups. There was no abnormal differentiation or tumor formation in various organs of rats in any group. (2) Compared with saline-treated animals, those treated with human umbilical cord mesenchymal stem cells showed significant functional recovery and reduced infarct volume, with no significant differences between different human umbilical cord mesenchymal stem cell doses. (3) Human umbilical cord mesenchymal stem cells were found in the ischemic brain after 14 and 28 days of follow-up, and the number of positive cells significantly decreased over time. (4) Neuronal nuclei expression in the human umbilical cord mesenchymal stem cell group was greater than that in the saline group, while glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 expression levels decreased. (5) Human umbilical cord mesenchymal stem cell treatment increased the number of CD31+ microvessels and doublecortin-positive cells after ischemic stroke. Human umbilical cord mesenchymal stem cells also upregulated the expression of CD31+/Ki67+. (6) At 14 days after intrathecal administration, brain-derived neurotrophic factor expression in the peri-infarct area and the concentrations of brain-derived neurotrophic factor in the cerebrospinal fluid in both human umbilical cord mesenchymal stem cell groups were significantly greater than those in the saline group and persisted until the 28th day. Taken together, these results indicate that the intrathecal administration of human umbilical cord mesenchymal stem cells via cerebellomedullary cistern injection is safe and effective for the treatment of ischemic stroke in rats. The mechanisms may include alleviating the local inflammatory response in the peri-infarct region, promoting neurogenesis and angiogenesis, and enhancing the production of neurotrophic factors.

Ischemic stroke: reflexology in complex treatment and rehabilitation of patients

Purpose of study.Stroke is one of the most important medical and social problems, both in the world and in Russia, which is due to high morbidity, mortality, and disability [1, 2, 3, 4, 5, 6, 7, 8, 9, 10]. According to WHO, stroke is the second leading cause of death in the world [11]. Over the past 30 years, the incidence has increased by 70 %; prevalence — 85 %; mortality increased by 43 % [12]. Statistical analysis data indicate that stroke affects about 0.5 million people in Russia every year, the rate is 3 per 1000 population [2]. The high level of disability (3.2 per 1000 population) is primarily due to the severity of neurological disorders that are difficult to correct [13]. Data from the National Stroke Registry show that 31 % of stroke patients require assistance for personal care; 20 % cannot move independently; only 8 % of surviving patients can return to their previous work [13]. Schemic stroke accounts for up to 85 % of all types of cerebrovascular accidents [8, 10]. The purpose of the presented scientific review is to acquaint doctors of various specialties with the possibilities of reflexology and justify the need to include this method in complex treatment, preventive and rehabilitation protocols for ischemic stroke to restore functionality and resume the most active social and everyday activities, improving the quality of life of this category of patients [1, 3, 14]. Conclusions: This article discusses an integrated approach to the management of post-stroke patients with the inclusion of reflexology in treatment and rehabilitation protocols along with the necessary pharmaceutical therapy and other rehabilitation methods. Particular attention is paid to the use of reflexology for the prevention of strokes. To solve these problems, an analysis of domestic and foreign medical literature devoted to this issue was carried out.

Abstract 4120957: Endovascular Thrombectomy Versus Medical Management for Acute Ischemic Stroke with Large Infarct: An Updated Meta-Analysis of Randomized Controlled Trials

Background: Endovascular therapy (EVT) has revolutionized the treatment of acute ischemic stroke due to large vessel occlusions. Despite the increasing evidence for EVT, its efficacy remains understudied in patients with acute ischemic stroke with large infarcts. Patients with large-volume ischemic strokes are excluded from major randomized controlled trials (RCTs) despite contributing up to 25% of all acute ischemic strokes. Aim: This study aimed to compare clinical outcomes with endovascular thrombectomy versus medical management in patients with acute ischemic stroke with large infarct. Methods: We conducted a systematic literature review on PubMed, Embase, Scopus and Cochrane Library from inception to 15th May 2024 for RCTs. The inverse-variance random-effects model was used to pool odds ratio (OR) and risk ratio (RR) with 95% confidence intervals. The statistical significance was set at p&lt;0.05. Results: 6 RCTs with 1887 patients (945: EVT and 942: medical management) were included. The mean age in both EVT and medical management groups was 70 ± 11.4 years. EVT was associated with a better modified Rankin Score (mRS) at 90 days [OR: 1.68; 95% CI: 1.38, 2.04; p&lt;0.00001], mRS at 90 days (0-2) [OR: 2.47; 95% CI: 1.87, 3.27; p&lt;0.00001], mRS at 90 days (0-3) [OR: 1.96; 95% CI: 1.56, 2.46; p&lt;0.00001], and early neurological improvement [RR: 2.35; 95% CI: 1.79, 3.10; p&lt;0.00001] compared to medical management. EVT was also associated with a higher risk of symptomatic intracranial hemorrhage [RR: 1.71; 95% CI: 1.09, 2.66; p=0.02]. The 90-day mortality [RR: 0.86; 95% CI: 0.72, 1.02; p=0.08] was comparable between the two groups. Conclusion: Patients with acute ischemic stroke with large infarct had superior functional outcomes with EVT as compared to medical management alone. However, EVT was associated with higher risks of symptomatic intracranial hemorrhage, with comparable 90-day mortality risk. Further large RCTs are warranted to evaluate the outcomes with EVT in acute ischemic stroke with large infarct.

Mesenchymal Stem Cell Therapy to Reduce the Neurological Deficit of Chronic Ischemic Stroke Patients: A Systematic Review

Current ischemic and hemorrhagic stroke treatments are limited by a narrow golden period and lack of regenerative benefits, so stem cell therapy emerges as an ideal candidate for functional recovery in stroke patients. Stem cell therapy, still being studied, is expected to repair ischemic areas damaged by stroke to restore their physiological functions and reduce neurological deficits in chronic stroke patients. This study aimed to determine the therapeutic efficacy of MSCs in reducing neurological deficits in chronic ischemic stroke patients. We conducted a systematic review. We searched PubMed, Cochrane Library, Science Direct, and Springer Link from inception until December 2022 for cohort studies dealing with mesenchymal stem cell therapy for patients with ischemic stroke. The citation-searching method in this study collected 1,038 articles using the advanced searching method and 8 articles using the citation-searching method, bringing the total number of articles to 1,046. The exclusion criteria used were articles with systematic reviews and meta-analyses and articles that were not accessible in full text. Based on the results of a systematic review study conducted, the conclusion that can be drawn is that MSCs therapy has proven effective in reducing neurological deficits in chronic ischemic stroke patients in terms of the decreased NIHSS score.

Rationale and design of the efficacy and safety of combination of cilostazol and gingko biloba extract EGb 761 in patients with acute non-cardioembolic ischemic stroke (RENEW): A pilot and feasibility randomized controlled trial

BackgroundDual antiplatelet therapy with aspirin and clopidogrel is the standard treatment for acute ischemic stroke (AIS). Cilostazol has emerged as a safe alternative with pleiotropic effects that prevent stroke without increasing the risk of bleeding and has been shown to reduce neurological deterioration (ND) in the acute phase. Ginkgo biloba extract (EGb 761) has also been reported to improve neurological impairment following AIS. This trial aimed to evaluate the efficacy and safety of the combination of cilostazol and EGb 761 in reducing early stroke recurrence and ND in patients with non-cardioembolic AIS. MethodsThe RENEW trial is a prospective, randomized, active-controlled, double-blind, parallel, multicenter phase IV study. Five hundred patients with non-cardioembolic AIS presenting within 72 h of symptom onset will be randomized to receive either aspirin 100 mg and cilostazol 200 mg plus EGb 761 160 mg daily or aspirin 100 mg and clopidogrel 75 mg daily for 90 days. The primary outcomes included the combined ND rate during hospitalization and stroke recurrence within 90 days. Secondary outcomes included the rates of ND, recurrent AIS, hemorrhagic stroke, hemorrhagic transformation, functional outcomes (modified Rankin Scale 0–2), bleeding events, and changes in the dizziness handicap inventory scores. DiscussionThe RENEW trial is expected to provide evidence for the safety and efficacy of combining aspirin, cilostazol, and EGb 761 as an alternative to standard therapy for the acute management of non-cardioembolic AIS. Trial RegistrationThis trial was registered at ClinicalTrials.gov (NCT05445895).

Minimally Invasive Syringe-Injectable Hydrogel with Angiogenic Factors for Ischemic Stroke Treatment.

Ischemic stroke (IS) accounts for most stroke incidents and causes intractable damage to brain tissue. This condition manifests as diverse aftereffects, such as motor impairment, emotional disturbances, and dementia. However, a fundamental approach to curing IS remains unclear. This study proposes a novel approach for treating IS by employing minimally invasive and injectable jammed gelatin-norbornene nanofibrous hydrogels (GNF) infused with growth factors (GFs). The developed GNF/GF hydrogels are administered to the motor cortex of a rat IS model to evaluate their therapeutic effects on IS-induced motor dysfunction. GNFs mimic a natural fibrous extracellular matrix architecture and can be precisely injected into a targeted brain area. The syringe-injectable jammed nanofibrous hydrogel system increased angiogenesis, inflammation, and sensorimotor function in the IS-affected brain. For clinical applications, the biocompatible GNF hydrogel has the potential to efficiently load disease-specific drugs, enabling targeted therapy for treating a wide range of neurological diseases.

Comparative analysis of the efficacy and safety of non-immunogenic staphylokinase and alteplase in bridging therapy of ischemic stroke

Introduction. Bridging therapy is the main method of treating ischemic stroke (IS) due to proximal occlusion, the effectiveness of which depends on the speed of its implementation. It is possible to increase the speed of systemic thrombolytic therapy (STT) and reduce the delay before mechanical thrombectomy (MT) by using bolus forms of thrombolytic drugs.Aim. To evaluate the efficacy and safety of using non-immunogenic staphylokinase compared to alteplase in bridging therapy of IS in real clinical practice of a regional stroke center (RSC).Materials and methods. A retrospective study of the combined use of STT and MT for the treatment of IS due to proximal occlusion was conducted from the reperfusion therapy registry of the RSC of the Tomsk Regional Clinical Hospital from 2017 to 2023. The final analysis included 49 patients who received non-immunogenic staphylokinase and 26 patients who received alteplase.Results. The time between the stages of bridging therapy was 92.0 [65.0–130.0] min in the non-immunogenic staphylokinase group and 35.0 [25.0–50.0] min in the alteplase group (p &lt; 0.001). No intergroup differences were found in the incidence of symptomatic hemorrhagic transformation: 8.1% in the non-immunogenic staphylokinase group and 3.8% in the alteplase group (p = 0.476). Mortality in both groups did not differ significantly and was 30.6% and 26.9%, respectively. Favorable functional outcome was observed in 40.8% of patients in the non-immunogenic staphylokinase group and in 23.1% in the alteplase group (p = 0.151).Conclusion. Comparable efficacy and safety of non-immunogenic staphylokinase and alteplase in the context of staged reperfusion therapy were revealed. The use of non-immunogenic staphylokinase is associated with a decrease in the time between the stages of bridging therapy.