Stroke Therapy Research Articles

Mesoporous manganese-doped nano-antioxidant suppresses pyroptosis for effective ischemic stroke therapy

Pyroptosis mediates neuroinflammation following ischemic stroke and contributes to its development, indicating that targeting pyroptosis-related pathways could be a potential therapeutic strategy for stroke. In this study, a mesoporous manganese-doped cerium oxide (MMC) nano-antioxidant encapsulated with caspase-1 inhibitor VX765 is rationally designed and engineered to relieve ischemic stroke by integrating the suppression of pyroptosis activity with reactive oxygen species (ROS) scavenging capability. Through the surface modification of Angiopoietin-2 (Ang2), the nano-antioxidant can specifically bind to the low-density lipoprotein receptor-related protein, cross the blood–brain barrier, and ultimately aggregate in ischemic neuronal tissues. In mice subjected to middle cerebral artery occlusion/reperfusion, the nano-antioxidant alleviates oxidative stress, inhibits cell pyroptosis, reduces inflammatory cytokines, and regulates microglial polarization toward M2, ultimately mitigating neuroinflammation and reperfusion injury in brain tissue. Mechanistic studies reveal that the pyroptosis-associated NOD-like receptor signaling pathway, the inflammation-associated TNF signaling pathway, the neutrophil chemotaxis-associated Toll-like receptor signaling pathway, and the oxidative stress-associated NF-kappa B signaling pathway are involved in the antioxidant-mediated stroke therapy. Endowed with pyroptosis-reversing ability and nano-antioxidant activities, this engineered antioxidant presents a novel therapeutic paradigm for minimizing reperfusion injury and enhancing stroke treatment efficacy.

Mitochondria-containing extracellular vesicles from mouse vs. human brain endothelial cells for ischemic stroke therapy

Ischemic stroke-induced mitochondrial dysfunction in the blood-brain barrier-forming brain endothelial cells (BECs) results in long-term neurological dysfunction post-stroke. We previously reported data from a pilot study where intravenous administration of human BEC (hBEC)-derived mitochondria-containing extracellular vesicles (EVs) showed a potential efficacy signal in a mouse middle cerebral artery occlusion (MCAo) model of stroke. We hypothesized that EVs harvested from donor species homologous to the recipient species (e.g., mouse) may improve therapeutic efficacy, and therefore, use of mouse BEC (mBEC)-derived EVs may improve post-stroke outcomes in MCAo mice.We investigated potential differences in the mitochondria transfer of EVs derived from the same species as the recipient cell (mBEC-EVs and recipient mBECs or hBECs-EVs and recipient hBECs) vs. cross-species EVs and recipient cells (mBEC-EVs and recipient hBECs or vice versa). Our results showed that while both hBEC- and mBEC-EVs transferred EV mitochondria, mBEC-EVs outperformed hBEC-EVs in increasing ATP levels and improved recipient mBEC mitochondrial function via increasing oxygen consumption rates. mBEC-EVs significantly reduced brain infarct volume and neurological deficit scores compared to vehicle-injected MCAo mice. The superior therapeutic efficacy of mBEC-EVs in MCAo mice support the continued use of mBEC-EVs to optimize the therapeutic potential of mitochondria-containing EVs in preclinical mouse models.

Microglial heterogeneity in the ischemic stroke mouse brain of both sexes

BackgroundIschemic stroke elicits a complex and sustained immune response in the brain. Immunomodulatory treatments have long held promise for improving stroke outcomes, yet none have succeeded in the clinical setting. This lack of success is largely due to our incomplete understanding of how immune cells respond to stroke. The objective of the current study was to dissect the effect of permanent stroke on microglia, the resident immune cells within the brain parenchyma.MethodsA permanent middle cerebral artery occlusion (pMCAO) model was used to induce ischemic stroke in young male and female mice. Microglia were sorted from fluorescence reporter mice after pMCAO or sham surgery and then subjected to single-cell RNA sequencing analysis. Various methods, including flow cytometry, RNA in situ hybridization, immunohistochemistry, whole-brain imaging, and bone marrow transplantation, were also employed to dissect the microglial response to stroke. Stroke outcomes were evaluated by infarct size and behavioral tests.ResultsFirst, we showed the morphologic and spatial changes in microglia after stroke. We then performed single-cell RNA sequencing analysis on microglia isolated from sham and stroke mice of both sexes. The data indicate no major sexual dimorphism in the microglial response to permanent stroke. Notably, we identified seven potential stroke-associated microglial clusters, including four major clusters characterized by a disease-associated microglia-like signature, a highly proliferative state, a macrophage-like profile, and an interferon (IFN) response signature, respectively. Importantly, we provided evidence that the macrophage-like cluster may represent the long-sought stroke-induced microglia subpopulation with increased CD45 expression. Lastly, given that the IFN-responsive subset constitutes the most prominent microglial population in the stroke brain, we used fludarabine to pharmacologically target STAT1 signaling and found that fludarabine treatment improved long-term stroke outcome.ConclusionsOur findings shed new light on microglia heterogeneity in stroke pathology and underscore the potential of targeting specific microglial populations for effective stroke therapies.

Angioedema Secondary to Tenecteplase Use in a Patient with Acute Ischemic Stroke: A Case Report.

Angioedema, a swelling of the subcutaneous or submucosal layers of the skin or gastrointestinal tract, is a potential complication to thrombolytic therapy in the treatment of acute ischemic strokes. In these cases, angioedema develops due to increased levels of bradykinin as a result of the activation of the fibrinolytic pathway and contact activation system. Angioedema can involve the tongue, larynx, and vocal cords, leading to occlusion of the airway and death due to asphyxiation. It is vital for the emergency physician to know that this complication can occur to ensure appropriate monitoring for development of angioedema. We report the case of a 65-year-old Black man who presented with signs of an acute ischemic stroke and was treated with tenecteplase. The patient's stroke symptoms mostly resolved within 90 minutes; however, he developed swelling of his right upper lip consistent with angioedema. The patient was treated with steroids and antihistamines. He was closely monitored and did not require airway intervention. The angioedema was almost fully resolved by the following day. Angioedema is a known complication of thrombolytic therapy for acute ischemic stroke. Risk factors for alteplase-associated angioedema include use of angiotensin-converting enzyme inhibitors, female gender, diabetes, and infarcts of the insula and frontal cortex. As hospital systems switch from alteplase to tenecteplase for the treatment of acute ischemic strokes for reasons of cost and ease of administration, it is important to recognize that angioedema is also a potential complication of tenecteplase.

Constraint-Induced Movement Therapy in Pediatric Stroke: Clinical Landscape & Implementation Barriers

Abstract Date Presented 03/22/24 This study describes the current landscape of constraint-induced movement therapy (CIMT) in the United States, with a focus on identifying barriers to its broader implementation to increase access to this underutilized intervention. Primary Author and Speaker: Sophia Larson Contributing Authors: Hunter Moore, Alyssa Smith, Bhooma Aravamuthan, Sharon Ramey, Catherine Hoyt

Hyperacute ischemic stroke care-Current treatment and future directions.

A decade on from the first positive thrombectomy trials, hyperacute therapies for ischemic stroke continue to rapidly advance. Effective treatments remain limited to reperfusion, although several cytoprotective approaches continue to be investigated. Intravenous fibrinolytics are now demonstrated to be beneficial up to 24 h in patients selected using perfusion imaging, but their role in patients with non-disabling symptoms appears very limited. Tenecteplase is superior to alteplase in meta-analysis of the latest trials, and adjuvant thrombolytics are an area of active investigation. Endovascular thrombectomy is beneficial in a wide range of anterior and posterior circulation large vessel occlusions up to 24 h after onset with the more distal occlusions, mild presentations, and >24 h window being the main frontiers to be tested in ongoing trials. Imaging parameters are prognostic but appear not to modify the relative treatment benefit of thrombectomy versus standard medical care. Therefore, deciding who not to treat with thrombectomy is a key clinical challenge that requires careful but rapid integration of clinical, imaging, and patient preference considerations. Systems of care to accelerate delivery of these highly effective therapies will maximize benefits for the greatest number of patients with stroke.

Peripheral, but not central, IGF-1 treatment attenuates stroke-induced cognitive impairment in middle-aged female Sprague Dawley rats: The gut as a therapeutic target

Stroke results in immediate sensory or motor disability and increases the risk for long term cognitive-affective impairments. Thus, therapies are urgently needed to improve quality of life for stroke survivors, especially women who are at a greater risk for severe stroke after menopause. Most current research on stroke therapies target the central nervous system; however, stroke also impacts peripheral organ systems. Our studies using acyclic (estrogen-deficient) middle aged female Sprague Dawley rats show that this group not only displays worse outcomes after stroke as compared to adult females, but also has lower levels of the neuroprotective peptide Insulin-like Growth Factor (IGF1) in circulation. Intracerebroventricular (ICV) administration of IGF1 to this group decreases infarct volume and improves sensory motor performance in the acute phase. In this study, we show that, despite this neuroprotection, ICV-IGF1 did not reduce peripheral inflammation or improve post stroke cognitive impairment in the chronic phase. In view of the evidence that stroke induces rapid gut dysfunction, we tested whether systemic delivery of IGF1 (intraperitoneal, IP) would promote gut health and consequently improve long-term behavioral outcomes. Surprisingly, while IP-IGF1, delivered 4 h and 24 h after ischemic stroke, did not reduce infarct volume or acute sensory motor impairment, it significantly attenuated circulating levels of pro-inflammatory cytokines, and attenuated stroke-induced cognitive impairment. In addition, IP-IGF1 treatment reduced gut dysmorphology and gut dysbiosis. Our data support the conclusion that therapeutics targeting peripheral targets are critical for long-term stroke recovery, and that gut repair is a novel therapeutic target to improve brain health in aging females.

Revascularization Therapies for Ischemic Stroke and Association With Risk of Epilepsy: A Danish Nationwide Register-Based Study.

The association between stroke revascularization therapies and poststroke epilepsy is only sparsely investigated, and results are conflicting. The aim of this study is to investigate whether stroke revascularization therapies are associated with different risks of poststroke epilepsy. We conducted a nationwide, register-based, propensity score-matched cohort study. We identified 40 816 patients admitted with a first ischemic stroke and no prior history of epilepsy in Denmark between January 1, 2011, and December 16, 2018. Of these, 6541 were treated with thrombolysis, 379 with thrombectomy, and 1005 with both thrombolysis and thrombectomy. The 3 treatment groups were each matched 1:1 to patients with stroke not treated with revascularization. Exact matching was done for sex, while propensity scores included information on stroke severity, cortical involvement, age, comorbidities, and socioeconomic parameters. Outcome was any diagnosis of epilepsy. We used Cox regressions to estimate adjusted hazard ratios (HRs) of epilepsy after ischemic stroke. Compared with matched patients with ischemic stroke not receiving revascularization treatment, patients who received thrombolysis alone had 32% lower risk of epilepsy (adjusted HR, 0.68 [95% CI, 0.57-0.81]) and patients who received thrombolysis and thrombectomy had 45% lower risk of epilepsy (adjusted HR, 0.55 [95% CI, 0.41-0.73]). Thrombectomy alone was not associated with significantly lower risk of epilepsy compared with matched patients with ischemic stroke not receiving revascularization therapy (adjusted HR, 0.78 [95% CI, 0.57-1.29]). Thrombolysis alone and in combination with thrombectomy in ischemic stroke was associated with lower risk of epilepsy, whereas thrombectomy alone was not associated with lower risk of epilepsy.

Modified Rankin Scale disability status at day 4 poststroke is an informative predictor of long-term day 90 outcome

BackgroundLong-term disability after stroke is standardly assessed 3 months post-onset, using the modified Rankin Scale (mRS). The value of an early, day 4 mRS assessment for projecting the 3-month disability outcome has not been formally investigated. MethodsIn this cohort of patients with acute cerebral ischemia and intracranial hemorrhage, we analyzed day 4 and day 90 mRS assessments in the NIH Field Administration of Stroke Therapy– Magnesium (FAST-MAG) Phase 3 trial. The performance of day 4 mRS, alone and as part of multivariate models, in predicting day 90 mRS was assessed using correlation coefficients, percent agreement, and the kappa statistics. ResultsAmong the 1573 acute cerebrovascular disease (ACVD) patients, 1206 (76.7%) had acute cerebral ischemia (ACI), while 367 (23.3%) had intracranial hemorrhage. Among all 1573 ACVD patients, day 4 mRS and day 90 mRS correlated strongly, Spearman's rho=0.79, in unadjusted analysis with weighted kappa of 0.59. For dichotomized outcomes, simple carry-forward of the day 4 mRS performed fairly well in agreeing with day 90 mRS: mRS 0-1 (kappa=0.67), 85.4%; mRS 0-2 (k=0.59), 79.5%; fatal outcome, 88% (k=0.33). Correlations of 4d and 90d mRS were stronger for ACI than ICH patients, 0.76 vs 0.71. ConclusionsIn this acute cerebrovascular disease patient cohort, assessment of global disability performed on day 4 is highly informative regarding long-term, 3-month mRS disability outcome, alone, and even more strongly in combination with baseline prognostic variables. The day 4 mRS is a useful measure for imputing the final patient disability outcome in clinical trials and quality improvement programs.

Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke: a special outlook on mitochondrial delivery.

Ischemic stroke is a secondary cause of mortality worldwide, imposing considerable medical and economic burdens on society. Extracellular vesicles, serving as natural nano-carriers for drug delivery, exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke. However, the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency. By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles, their delivery efficacy may be greatly improved. Furthermore, previous studies have indicated that microvesicles, a subset of large-sized extracellular vesicles, can transport mitochondria to neighboring cells, thereby aiding in the restoration of mitochondrial function post-ischemic stroke. Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components, such as proteins or deoxyribonucleic acid, or their sub-components, for extracellular vesicle-based ischemic stroke therapy. In this review, we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies. Given the complex facets of treating ischemic stroke, we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process. Moreover, given the burgeoning interest in mitochondrial delivery, we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.

Pengaruh Terapi Kepalan Bola dalam Peningkatan Kemampuan Fungsi Saraf pada Penderita Stroke Iskemik

Functional disorders, also known as strokes, are conditions when blood flow to the brain is blocked and cannot reach the brain cells, resulting in paralysis of the nerves (neurological deficit) and even death. Stroke is a clinical symptom of loss of function of the central nervous system that develops and attacks quickly. The uncontrollability of nerve signals to the muscles is caused by damage to parts of the brain. As you get older, you are at risk of having a stroke. Judging from the cause, strokes are divided into two types, including hemorrhagic strokes which are caused by rupture of cerebral blood vessels, while ischemic strokes are caused by thrombus or embolism in the cerebral blood vessels. The causes of stroke consist of factors that can be changed and factors that cannot be changed. This study aims to determine the effect of ball fist therapy on improving the ability of nerve function in the upper limbs. Literature review is the method used in preparing this research. Literature reviews are carried out on research articles, journals, books and other sources. The results stated that there was an increase in the ability of nerve function in the upper limbs after ball fist therapy was carried out for approximately one month with routine ball fist therapy in stroke patients.the contents of this template, please backup it first.

Predictive Factors for Altered Quality of Life in Patients with Type 2 Diabetes Mellitus.

Objectives: To evaluate the quality of life (QoL) in a group of patients with type 2 diabetes (T2DM) and to identify predictive factors to apply the necessary measures to improve it. Methods: For this, 299 patients with T2DM were enrolled in a cross-sectional study, and their QoL was assessed using the EQ-5D-3L questionnaire. All patients underwent clinical exams, routine laboratory tests, and nerve conduction velocity (NCV) at the common peroneal nerve. Results: Patients had a median age of 66 (57; 70) years, median duration of T2DM of 10 (6; 15) years, median HbA1c of 8 (7; 9.3)%, and mean EQ-5D-3L score of 55%. In addition, 9.7% presented extreme difficulty in mobility, 18.5% severe difficulty in self-care, and 16.4% in usual activities. One-third presented with severe pain or discomfort, anxiety, or depression (level 3 EQ-5D-3L). DPN, heart failure (HF), cerebral stroke, and insulin therapy increased the likelihood of a reduced QoL (EQ-5D-3L < 50). The EQ-5D-3L score inversely correlated with serum creatinine, glycemic control, lipid profile, diabetes duration, age, mobility, self-care, pain/discomfort, usual activities, and anxiety/depression and positively correlated with NCV, HDLc, and eGFR. Conclusions: Preventing neuropathic complications, chronic kidney disease, stroke, and HF and obtaining the glycemic and lipid targets could improve the QoL in patients with T2DM.

Artificial Intelligence-based automated CT brain interpretation to accelerate treatment for acute stroke in rural India: An interrupted time series study.

In resource-limited settings, timely treatment of acute stroke is dependent upon accurate diagnosis that draws on non-contrast computed tomography (NCCT) scans of the head. Artificial Intelligence (AI) based devices may be able to assist non-specialist physicians in NCCT interpretation, thereby enabling faster interventions for acute stroke patients in these settings. We evaluated the impact of an AI device by comparing the time to intervention (TTI) from NCCT imaging to significant intervention before (baseline) and after the deployment of AI, in patients diagnosed with stroke (ischemic or hemorrhagic) through a retrospective interrupted time series analysis at a rural hospital managed by non-specialists in India. Significant intervention was defined as thrombolysis or antiplatelet therapy in ischemic strokes, and mannitol for hemorrhagic strokes or mass effect. We also evaluated the diagnostic accuracy of the software using the teleradiologists' reports as ground truth. Impact analysis in a total of 174 stroke patients (72 in baseline and 102 after deployment) demonstrated a significant reduction of median TTI from 80 minutes (IQR: 56·8-139·5) during baseline to 58·50 (IQR: 30·3-118.2) minutes after AI deployment (Wilcoxon rank sum test-location shift: -21·0, 95% CI: -38·0, -7·0). Diagnostic accuracy evaluation in a total of 864 NCCT scans demonstrated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) in detecting intracranial hemorrhage to be 0·89 (95% CI: 0·83-0·93), 0·99 (0·98-1·00), 0·96 (0·91-0·98) and 0·97 (0·96-0·98) respectively, and for infarct these were 0·84 (0·79-0·89), 0·81 (0·77-0·84), 0·58 (0·52-0·63), and 0·94 (0·92-0·96), respectively. AI-based NCCT interpretation supported faster abnormality detection with high accuracy, resulting in persons with acute stroke receiving significantly earlier treatment. Our results suggest that AI-based NCCT interpretation can potentially improve uptake of lifesaving interventions for acute stroke in resource-limited settings.

Temporal trends of sex differences in acute reperfusion therapy and early outcomes of acute ischemic stroke in South Korea: 10-year analysis of the nationwide stroke registry.

Sex differences in stroke outcomes are notable, with women experiencing higher incidence rates, greater disability-adjusted life years, and poorer recovery compared to men, even after adjusting for age and comorbidities. Despite the disproportionate burden in women, studies have reported that women are less likely to receive appropriate stroke treatment than men. This study investigated temporal trends of sex differences in acute reperfusion therapy and early outcomes in patients with acute ischemic stroke over 10 years in South Korea. A retrospective analysis of Korean Stroke Registry included patients with acute ischemic stroke from 2012 to 2021. The study outcomes were the temporal trends of acute reperfusion therapy and early outcomes over 10 years in men and women, respectively. In addition, this study analyzed the temporal trends of sex differences in these parameters during the same period. Early outcomes include the proportions of favorable functional outcomes at discharge, discharge patterns, and in-hospital mortality. A total of 93,692 patients (68.4 years, 40.1% women) with acute ischemic stroke were finally enrolled. Women had a higher age at stroke onset, a higher prevalence of atrial fibrillation, and more severe strokes than men. Women had lower proportion of favorable functional outcomes at discharge and higher proportion of in-hospital mortality compared to men each year. The proportion of patients who received intravenous thrombolysis was lower or similar in women compared to men in most years, and the proportion of patients who received endovascular thrombectomy did not significantly differ between sexes annually. Sex differences in acute reperfusion therapy remained unchanged over 10 years. Women have received acute reperfusion therapy at similar or lower rates than men and experienced poorer outcomes, despite having more stroke risk factors and often more severe strokes.

External Validation of a Model for Persistent Perfusion Deficit in Patients With Incomplete Reperfusion After Thrombectomy: EXTEND-PROCEED.

We recently developed a model (PROCEED) that predicts the occurrence of persistent perfusion deficit (PPD) at 24 hours in patients with incomplete angiographic reperfusion after thrombectomy. This study aims to externally validate the PROCEED model using prospectively acquired multicenter data. Individual patient data for external validation were obtained from the Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection, Tenecteplase versus Alteplase Before Endovascular Therapy for Ischemic Stroke part 1 and 2 trials, and a prospective cohort of the Medical University of Graz. The model's primary outcome was the occurrence of PPD, defined as a focal, wedge-shaped perfusion delay on 24-hour follow-up perfusion imaging that corresponds to the capillary phase deficit on last angiographic series in patients with <Thrombolysis in Cerebral Infarction 3 reperfusion after thrombectomy. The model's performance was evaluated with discrimination, calibration accuracy, and clinical decision curves. We included 371 patients (38% with PPD). The externally validated model had good discrimination (C-statistic 0.81, 95% CI 0.77-0.86) and adequate calibration (intercept 0.25, 95% CI 0.21-0.29 and slope 0.98, 95% CI 0.90-1.12). Across a wide range of probability thresholds (i.e., depending on the physicians' preferences on how the model should be used), the model shows net benefit on clinical decision curves, informing physicians on the likelihood of PPD. If a physician's attitude toward false-positive and false-negative ratings is equal, the model would reduce 13 in 100 unnecessary interventions by correctly predicting complete delayed reperfusion, without missing a patient with PPD. The externally validated model had adequate predictive accuracy and discrimination. Depending on the acceptable threshold probability, the model accurately predicts persistent incomplete reperfusion and may advise physicians whether additional reperfusion attempts should be performed.

Endovascular therapy versus best medical management in distal medium middle cerebral artery acute ischaemic stroke: a multinational multicentre propensity score-matched study

BackgroundThe efficacy of endovascular treatment (EVT) in acute ischaemic stroke due to distal medium vessel occlusion (DMVO) remains uncertain. Our study aimed to evaluate the safety and efficacy of EVT...

Comparison of anesthesia methods for intra-arterial therapy of patients with acute ischemic stroke: an updated meta-analysis and systematic review

ObjectivesCurrently, there remains debate regarding the optimal anesthesia approach for patients undergoing intra-arterial therapy for acute ischemic stroke. Therefore, we conducted a comparative analysis to assess the effects of general anesthesia versus non general anesthesia on patient outcomes.MethodsThe research methodology entailed comprehensive searches of prominent databases such as the Cochrane Library, PubMed, Scopus, and Web of Science, covering the period from January 1, 2010, to March 1, 2024. Data synthesis employed techniques like risk ratio or standardized mean difference, along with 95% confidence intervals. The study protocol was prospectively registered with PROSPERO (CRD42024523079).ResultsA total of 27 trials and 12,875 patients were included in this study. The findings indicated that opting for non-general anesthesia significantly decreased the risk of in-hospital mortality (RR, 1.98; 95% CI: 1.50 to 2.61; p<0.00001; I2 = 20%), as well as mortality within three months post-procedure (RR, 1.24; 95% CI: 1.15 to 1.34; p<0.00001; I2 = 26%), while also leading to a shorter hospitalization duration (SMD, 0.24; 95% CI: 0.15 to 0.33; p<0.00001; I2 = 44%).ConclusionIschemic stroke patients who undergo intra-arterial treatment without general anesthesia have a lower risk of postoperative adverse events and less short-term neurological damage. In routine and non-emergency situations, non-general anesthetic options may be more suitable for intra-arterial treatment, offering greater benefits to patients. In addition to this, the neuroprotective effects of anesthetic drugs should be considered more preoperatively and postoperatively.

Hydrogel-Based Therapies for Ischemic and Hemorrhagic Stroke: A Comprehensive Review.

Stroke remains the second leading cause of death and a major cause of disability worldwide, significantly impacting individuals, families, and healthcare systems. This neurological emergency can be triggered by ischemic events, including small vessel arteriolosclerosis, cardioembolism, and large artery atherothromboembolism, as well as hemorrhagic incidents resulting from macrovascular lesions, venous sinus thrombosis, or vascular malformations, leading to significant neuronal damage. The resultant motor impairment, cognitive dysfunction, and emotional disturbances underscore the urgent need for effective therapeutic interventions. Recent advancements in biomaterials, particularly hydrogels, offer promising new avenues for stroke management. Hydrogels, composed of three-dimensional networks of hydrophilic polymers, are notable for their ability to absorb and retain substantial amounts of water. Commonly used polymers in hydrogel formulations include natural polymers like alginate, chitosan, and collagen, as well as synthetic polymers such as polyethylene glycol (PEG), polyvinyl alcohol (PVA), and polyacrylamide. Their customizable characteristics-such as their porosity, swelling behavior, mechanical strength, and degradation rates-make hydrogels ideal for biomedical applications, including drug delivery, cell delivery, tissue engineering, and the controlled release of therapeutic agents. This review comprehensively explores hydrogel-based approaches to both ischemic and hemorrhagic stroke therapy, elucidating the mechanisms by which hydrogels provide neuroprotection. It covers their application in drug delivery systems, their role in reducing inflammation and secondary injury, and their potential to support neurogenesis and angiogenesis. It also discusses current advancements in hydrogel technology and the significant challenges in translating these innovations from research into clinical practice. Additionally, it emphasizes the limited number of clinical trials utilizing hydrogel therapies for stroke and addresses the associated limitations and constraints, underscoring the need for further research in this field.

Rasagiline Exerts Neuroprotection towards Oxygen-Glucose-Deprivation/Reoxygenation-Induced GAPDH-Mediated Cell Death by Activating Akt/Nrf2 Signaling.

Rasagiline (Azilect®) is a selective monoamine oxidase B (MAO-B) inhibitor that provides symptomatic benefits in Parkinson's disease (PD) treatment and has been found to exert preclinical neuroprotective effects. Here, we investigated the neuroprotective signaling pathways of acute rasagiline treatment for 22 h in PC12 neuronal cultures exposed to oxygen-glucose deprivation (OGD) for 4 h, followed by 18 h of reoxygenation (R), causing 40% aponecrotic cell death. In this study, 3-10 µM rasagiline induced dose-dependent neuroprotection of 20-80%, reduced the production of the neurotoxic reactive oxygen species by 15%, and reduced the nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by 75-90%. In addition, 10 µM rasagiline increased protein kinase B (Akt) phosphorylation by 50% and decreased the protein expression of the ischemia-induced α-synuclein protein by 50% in correlation with the neuroprotective effect. Treatment with 1-5 µM rasagiline induced nuclear shuttling of transcription factor Nrf2 by 40-90% and increased the mRNA levels of the antioxidant enzymes heme oxygenase-1, (NAD (P) H- quinone dehydrogenase, and catalase by 1.8-2.0-fold compared to OGD/R insult. These results indicate that rasagiline provides neuroprotection to the ischemic neuronal cultures through the inhibition of α-synuclein and GAPDH-mediated aponecrotic cell death, as well as via mitochondrial protection, by increasing mitochondria-specific antioxidant enzymes through a mechanism involving the Akt/Nrf2 redox-signaling pathway. These findings may be exploited for neuroprotective drug development in PD and stroke therapy.

Beyond stroke therapy, neuroaid (a chinese herbal) has an effect on cognition and neurogenesis, a bibliometric study

Introduction NeuroAiD, also known as MLC601 or MLC901, is a Chinese herbal combination used worldwide for stroke treatment. It contains herbal components and five hewan components. MLC601 contains herbal components and hewan components, while MLC901 has a similar herbal composition. NeuroAiD is used to support neurologic recovery after stroke and to aid cognitive function in Alzheimer’s disease. Studies show that NeuroAiD has potential in treating Alzheimer’s disease and is beneficial in both local and global stroke models and in the Kortikal culture. However, there is limited bibliometric research on NeuroAiD, which is a method of collecting data from published articles to analyze developments and trends in the field of research. This research contributes significantly to the literature and helps develop more effective stroke treatment strategies. Methods In this work, a literature review methodology is employed to gather data from the Scopus database using the keywords neuroaid. Data were analyzed using Biblioshiny and VOSviewer software to produce visualizations and bibliometric maps. We conducted quantitative and qualitative analysis Results The research trend found are documents by year, most relevant sources, factorial map of the most cited documents, factorial map of The documents with the highest contributes, documents by author, documents by country or territory, documents by subject area, documents by affiliation, network visualization, overlay visualization of scopus database using vosviewer, density visualization, thematic map, thematic evolution, topic dendogram, and world cloud. Conclusions The study investigates the potential of Neuroaid, a neuroprotective drug, for stroke prevention and cognitive function enhancement. It uses terms like “cognition” and “neurogenesis” to highlight its potential. While the study’s focus may be limited, it provides valuable insights into research direction and potential areas of neuroaid for stroke treatment.