Therapy For Ischemic Stroke Research Articles

Regulating astrocyte phenotype by Lcn2 inhibition toward ischemic stroke therapy.

Astrocytes can be reacted to "reactive astrocytes" after ischemia-reperfusion injury, in which A1 phenotype causes neuronal and oligodendrocyte death, whereas the A2 phenotype exerts neuroprotective effects, thus regulating reactive astrocyte to A2 type is a potential target for stroke therapy. Lcn2 level is highly associated with the phenotypic polarization of astrocytes. We found that silencing the Lcn2 gene by adeno-associated virus (AAV)-Lcn2 shRNA adenovirus resulted in a dramatic decrease in A1-type astrocytes and increase in A2 astrocytes in MCAO mice. Hence, a nanoplatform was developed for stroke therapy by inhibiting Lcn2. This system was fabricated by N-acetyl Pro-Gly-Pro peptide-decorated rod-shaped poly (lactic-co-glycolic acid) nanoparticles loading with rolipram (AP@R). The nanodrug can be efficiently taken up by neutrophils simultaneously through morphology-mediated passive targeting and Cxcr2 receptor-mediated active targeting, subsequently crossing the blood-brain barrier (BBB) by hitchhiking neutrophils. When accumulating at the brain parenchyma, the released rolipram can inhibit the Lcn2 level, thereby reversing the astrocyte phenotype to alleviate neuroinflammation and promote BBB repair. This work provides a new strategy for treating ischemic stroke.

Association Between Time to Treatment and Outcomes of Endovascular Therapy vs Medical Management in Patients With Large Ischemic Stroke.

Randomized trials have proven the benefit of endovascular therapy (EVT) for acute large ischemic stroke. This study was to characterize the effect of time to treatment on benefit of EVT vs medical management (MM) among patients with large ischemic stroke. This was a post hoc analysis of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core randomized trial. Patients who had an Alberta Stroke Program Early Computed Tomography Score of 3-5 or an ischemic core volume of 70-100 mL within 24 hours of symptom onset were treated with EVT plus MM or MM. Onset-to-expected arterial puncture time (OPT) was analyzed as a categorical variable (<6, 6-<12, and 12-24 hours) using binary logistic regression and as a continuous variable using a multivariable fractional polynomial interaction. The primary efficacy outcome was favorable outcomes (modified Rankin Scale scores 0-3) at 90 days. Safety outcomes included any intracranial hemorrhage (ICH), symptomatic ICH, and mortality. Among 451 patients (median age 68 years; 61.4% were men; median OPT 487 minutes [interquartile range 328-802]), 226 patients received EVT and 225 patients received MM. The EVT group showed higher rates of favorable outcomes than the MM group within OPT of 6 hours (44.4% vs 29.9%, adjusted odds ratio [aOR] 2.78, 95% CI 1.22-6.32) and 6-12 hours (45.7% vs 29.6%, aOR 2.39 [95% CI 1.21-4.71]), but not in OPT beyond 12 hours (51.6% vs 41.4%, aOR 2.05 [95% CI 0.88-4.77]). The benefit became nonsignificant after OPT of 13 hours and 22 minutes. In 3 OPT intervals, the rates of symptomatic ICH and mortality were similar between EVT and MM although the rate of any ICH increased. However, no interaction effect was found (all p interactions >0.10). These findings strengthen the benefit of EVT initiated within 13 hours and 22 minutes after symptom onset compared with MM alone in patients with large ischemic stroke, but EVT should not be withheld for patients presenting beyond 13 hours and 22 minutes. Pooled analysis of larger sample sizes is needed. ClinicalTrials.gov; NCT04551664. This study provides Class II evidence that EVT is associated with improved functional outcomes for acute large ischemic stroke within 24 hours after last known well, with no interaction by time.

Relationship between triglyceride-glucose index and intravenous thrombolysis outcomes for acute ischemic stroke

Aims: The aim of this study was to investigate the effect of triglyceride glucose index, a marker of insulin resistance, on early neurological deterioration (END), development of intracerebral hemorrhage and hemorrhagic transformation and mortality in patients receiving intravenous thrombolytic therapy for acute ischemic stroke. Methods: This retrospective study included 71 patients with acute ischemic stroke who received intravenous tissue plasminogen activator. Demographic data, clinical and radiological findings, fasting glucose and lipid profile, END, hemorrhage development and mortality rates were analyzed. We also calculated the triglyceride glucose (TyG) index and examined its correlation with early neurological deterioration, hemorrhage development and mortality. Results: The median age was 74 years (41-88), with a female predominance of 54.9%. The incidence of intracerebral hemorrhage was 9.6%, while END occurred in 39.6% of cases, and the 30-day mortality rate was 28.2%. The mean TyG index was 7.8 (2.8-27.6). The receiver operating characteristic curve analysis indicated that the TyG index predicted mortality with an area under the curve of 84.4%, a sensitivity of 85%, and a specificity of 82.35% in patients with a TyG index above 10.01 (p

Comparison of the safety and efficacy of dual antiplatelet therapy versus tenecteplase in patients with minor nondisabling acute ischemic stroke

To evaluate the safety and efficacy of dual antiplatelet therapy (DAPT) versus tenecteplase in minor non-disabling acute ischemic stroke. This retrospective observational study utilized data from our stroke database. All consecutive patients with minor non-disabling acute ischemic stroke treated with either DAPT or tenecteplase between January 2020 and June 2023 were included in the analysis. Of the 62 patients included in the analysis, the median (IQR) age was 66 (58–76) years, and 21 patients (34%) were female. Compared with patients receiving DAPT, those treated with tenecteplase were had higher NIHSS score at treatment (median [IQR], 4 [2–5] vs. 1 [1–2]; P = 0.01). At 90 days, 74.2% of patients (23/31) in the DAPT group and 71.0% (22/31) in the tenecteplase group had an excellent functional outcome (P = 0.78). Lower proportion of patients with minor bleeding events in DAPT group than tenecteplase group (3.2% [1/31] vs. 25.8% [8/31], P = 0.01). The findings in this study show that patients presenting with minor nondisabling acute ischemic stroke within 4.5 h of symptom onset, dual antiplatelet treatment was similar to intravenous tenecteplase with regard to excellent functional outcome at 90 days. However, more proportion of patients with bleeding events treated with tenecteplase.

Challenges and Outcomes of Thrombolytic Therapy in Acute Ischemic Stroke: The Iranian Perspective

Background: Acute ischemic stroke (AIS) is a leading cause of mortality and long-term disability worldwide. In Iran, AIS tends to occur nearly a decade earlier than in developed nations, presenting unique challenges. Intravenous recombinant tissue plasminogen activator (IV-rtPA) is an effective thrombolytic therapy for AIS, but various factors limit its utilization. Objectives: This study aimed to identify the barriers to the administration of IV-rtPA in AIS patients at Shahid Beheshti Hospital in Qom, Iran. Methods: A cross-sectional descriptive-analytical study was conducted on AIS patients admitted between November 2021 and September 2022. A total of 322 patients were screened, and 178 met the inclusion criteria. Data on demographic characteristics, stroke severity (NIHSS score), comorbidities, onset-to-door time, and reasons for not receiving IV-rtPA were analyzed using SPSS version 22. Results: Of the 178 patients, 87 (48.9%) received IV-rtPA, while 91 (51.1%) did not. The primary reasons for withholding thrombolysis were clinical improvement (37.4%), late hospital arrival beyond 4.5 hours (24.2%), lack of consent (20.9%), the physician's conservative approach (11%), and mild progression of stroke symptoms (6.6%). A significant correlation was found between NIHSS score and reasons for non-receipt of therapy (P &lt; 0.001). Patients with a prior stroke history were more likely to experience delays due to a physician’s conservative approach (28.6% vs. 5.7%, P &lt; 0.01). Barriers to thrombolysis were also associated with lower education levels and a lack of public awareness about stroke symptoms. Conclusions: Delayed hospital admission and lack of consent were the leading barriers to IV-rtPA administration. Public awareness campaigns emphasizing the urgency of recognizing stroke symptoms and seeking timely medical care are crucial to improving thrombolysis rates and reducing AIS-related disabilities in Iran.

Risk of Symptomatic Intracranial Hemorrhage After Mechanical Thrombectomy in Randomized Clinical Trials: A Systematic Review and Meta-Analysis.

Symptomatic intracranial hemorrhage (sICH) is the most dreaded complication after reperfusion therapy for acute ischemic stroke. We performed a meta-analysis of randomized controlled trials to estimate and compare risks of sICH after mechanical thrombectomy (MT) depending on the location of the large vessel occlusion, concomitant use of intravenous thrombolysis, timing of treatment, and core size. Randomized controlled trials were included, following a comprehensive search of different databases from inception to 1 March 2024. Random-effect models in a meta-analysis were employed to obtain the pooled risk ratios (RRs) and their corresponding 95% confidence intervals (95% CI) for sICH with MT, and were then compared to other reperfusion treatment regimens, including best medical treatment and intravenous thrombolysis (IVT). MT in the anterior circulation was associated with a significantly higher risk of sICH as compared with no-MT (RR: 1.46; 95%CI: 1.03-2.07; p = 0.037). The risk of sICH was comparable between the MT and MT+IVT groups (RR: 0.77; 95%CI: 0.57-1.03; p = 0.079). There was no difference in sICH risk with MT as compared with no-MT within 6 h of last known well (RR: 1.14; 95%CI: 0.78-1.66; p = 0.485) and beyond that time (RR: 1.29; 95%CI: 0.80-2.08; p = 0.252); the risk of sICH was also comparable between MT conducted within 6 h of last known well and MT conducted beyond that time (p = 0.512). The sICH risk for MT in the posterior circulation (RR: 7.48; 95%CI: 2.27-24.61) was significantly higher than for MT in the anterior circulation (RR: 1.18; 95%CI: 0.90-1.56) (p = 0.003). MT was also associated with a significantly higher sICH risk than no-MT among patients with large core strokes (RR: 1.71; 95%CI: 1.09-2.66, p = 0.018). When evaluating cumulative evidence from randomized controlled trials, the risk of sICH is increased after MT compared with patients not treated with MT. Yet, the difference is largely driven by the greater risk of sICH in patients treated with MT for posterior circulation occlusions and, to a lesser degree, large core strokes. Concomitant use of intravenous thrombolysis and the use of MT in the extended therapeutic window do not raise the risk of sICH.

The Role of Processed Electroencephalography in the Detection and Management of Acute Cerebral Ischemia: A Scoping Review.

Processed electroencephalography (pEEG) is increasingly used to titrate the depth of anesthesia. Whether such intra-procedural pEEG monitoring can offer additional information on cerebral perfusion or acute focal or global cerebral ischemia is unknown. This scoping review aimed to provide a narrative analysis of the current literature reporting the potential role of pEEG in adults with acute cerebral ischemia. In keeping with the scoping review methodology, a broad search strategy was defined, including descriptions of encephalography in acute ischemic stroke, carotid endarterectomy, cardiac surgery, and cardiac arrest. Additional screening of citations was conducted by 2 independent assessors. From 310 records, 28 full-text articles met inclusion criteria. Most identified studies were observational in design, and described the diagnostic ability of pEEG to identify cerebral hypoperfusion or its prognostic sensitivity after stroke or carotid surgery. No studies were identified that evaluated pEEG in the specific setting of endovascular therapy for acute ischemic stroke. Low sensitivity associations between pEEG indices and cerebral blood flow were highlighted, which may be influenced by cerebral autoregulatory thresholds. Despite the associations reported in observational studies, this review identified significant uncertainty in the role of pEEG during cerebral ischemia. There is a paucity of high-level observational (cohort or case-control) or randomized trial research examining the possible role of pEEG for the detection and management of cerebral ischemia during acute stroke, including during endovascular therapy, or in other common scenarios of acute cerebral ischemia.

The Efficacy of Intensive Statin Therapy in Acute Ischemic Stroke Following Intravenous Thrombolysis: The CASE II Study.

This study aimed to investigate the efficacy of early intensive statin therapy following intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS). AIS patients who received IVT and statin therapy were included from multicenter registry databases. The primary endpoint was functional independence, defined by a modified Rankin Scale (mRS) score of 0-2 at 90 days. Propensity score matching (PSM) analyses were employed. A total of 21,349 patients were included in this study, with a mean age of 68.5 ± 12.6 years, of whom 13,578 (63.6%) were male. The baseline NIHSS score was 4 (IQR 2-8). A total of 9532 patients (44.6%) received intensive statin therapy. In the PSM analysis, the proportion of patients with mRS scores of 0-2 was significantly higher in the intensive statin therapy group (OR = 1.095, 95% CI 1.022-1.173, p = 0.010). Statin type modified the effect of intensive statin therapy on functional independence (p-value for interaction = 0.030). Treatment effects favoring the intensive approach were observed in patients receiving atorvastatin (OR = 1.134, 95% CI 1.051-1.224, p = 0.001). Early intensive statin therapy following IVT leads to a significant but modest improvement in neurological outcomes, particularly in patients treated with atorvastatin as part of the intensive regimen.

Hemichorea-hemiballismus induced by intravenous thrombolytic therapy for acute ischemic stroke: a case report and literature review

Hemichorea-hemiballismus induced by intravenous thrombolytic therapy for acute ischemic stroke: a case report and literature review

Proton Pump Inhibitors Use in Patients With Ischemic Stroke on Dual Antiplatelet Therapy at Low Risk of Upper Gastrointestinal Bleeding.

Current guidelines lack recommendations regarding the use of proton pump inhibitors (PPIs) for preventing upper gastrointestinal bleeding (UGIB) among patients at low risk for UGIB treated with dual antiplatelet therapy for ischemic stroke (IS). Our objective was to assess the effectiveness of PPIs in lowering the risk of significant UGIB in this patient group. A retrospective cohort study was conducted involving patients at low risk for UGIB admitted for IS between 2014 and 2018 and treated with dual antiplatelet therapy. The study used a nationwide claims database in Korea. The primary end point was significant UGIB during 12 months after IS. To evaluate the risk of significant UGIB based on PPI use, we performed a multivariable Cox regression analysis. Subgroup analyses and propensity score matching analysis were conducted for validation. Among 96 722 patients with IS at low risk for UGIB who were on dual antiplatelet therapy (mean age, 67.0 years; men: 63.0%), 16 084 (16.6%) were treated with PPIs. During 12 months of follow-up, 325 patients experienced significant UGIB, and 479 experienced any UGIB. PPI use was associated with a reduced risk of significant UGIB (hazard ratio, 0.63 [95% CI, 0.45-0.89]; P=0.009). This association was consistent in the subgroup and propensity score matching analyses. In patients with IS receiving dual antiplatelet therapy, PPI use reduced the risk of significant UGIB by 37% on average, even among low-risk patients. However, the use of PPIs in this patient group was limited, highlighting the need for additional prospective studies.

Investigation into the Potential Mechanism of Radix Paeoniae Rubra Against Ischemic Stroke Based on Network Pharmacology.

Radix Paeoniae Rubra (RPR), an edible and medicinal Traditional Chinese Medicine (TCM), is extensively employed in therapeutic interventions of cardiovascular and cerebrovascular diseases. However, the curative effect of RPR on ischemic stroke remains ambiguous. This work integrated network pharmacology, molecular docking, and experimental validation to explore the mechanisms of RPR in treating ischemic stroke. In this study, we preliminarily elucidated the therapeutic effect and mechanism of RPR on ischemic stroke through network pharmacology, molecular docking analysis, and experimental verification. The results indicated that RPR improved the neurological deficit scores, decreased the size of infarcts, and reduced brain edema symptoms in the tMCAO mice model. Furthermore, through network pharmacology and molecular docking, four core targets (MAPK3, TNF-α, MAPK14, and JNK) closely related to RPR's treatment of ischemic stroke were identified, exhibiting strong affinity with two key active components of RPR: albiflorin (AF) and β-sitosterol (BSS). The Western blot showed the potential mechanism of RPR treatment for ischemic stroke by regulating the MAPK signaling pathway. Moreover, RPR and its main active ingredients exhibited a significant inhibitory effect on platelets. In conclusion, this study revealed that RPR alleviates ischemic injury by activating the MAPK signaling pathway, and its protective effect may partly stem from inhibiting platelet activation. This work may provide a scientific basis for the development and utilization of RPR as a natural edible material to prevent ischemic stroke and anti-platelet therapy.

Inhibition of Pyroptosis by Hydroxychloroquine as a Neuroprotective Strategy in Ischemic Stroke.

Hydroxychloroquine (HCQ), a well-known antimalarial and anti-inflammatory drug, has demonstrated potential neuroprotective effects in ischemic stroke by inhibiting pyroptosis, a programmed cell death associated with inflammation. This study investigates the impact of HCQ on ischemic stroke pathology using both in vivo and in vitro models. In vivo, C57BL/6 mice subjected to middle cerebral artery occlusion (MCAO) were treated with HCQ. Neurological deficits, infarct volume, and the expression of pyroptosis markers were evaluated. The results demonstrated that HCQ significantly improved motor function and reduced infarct volume in the MCAO mouse model. In vitro, BV2 microglial cells exposed to lipopolysaccharide (LPS) and oxygen-glucose deprivation (OGD) were treated with HCQ. Western blot and immunofluorescence analyses revealed that HCQ effectively suppressed the expression of pyroptosis markers GSDMD and NLRP3 in both in vivo and in vitro models. These findings suggest that HCQ mitigates ischemic stroke damage by inhibiting pyroptosis, highlighting its potential as a therapeutic agent for ischemic stroke. This study provides novel insights into the molecular mechanisms by which HCQ exerts its neuroprotective effects, offering a promising new avenue for developing safe, cost-effective, and widely applicable stroke treatments. The potential of HCQ to modulate neuroinflammatory pathways presents a significant advancement in ischemic stroke therapy, emphasizing the importance of targeting pyroptosis in stroke management and the broader implications for treating neuroinflammatory conditions.Significance Statement Ischemic stroke remains a leading cause of disability and death globally, with limited effective treatments. This study reveals that HCQ significantly mitigates ischemic stroke damage by inhibiting pyroptosis, a form of programmed cell death. Using in vivo and in vitro models, HCQ was shown to improve motor function and reduce infarct volume, highlighting its potential as a neuroprotective agent. These findings offer a promising new therapeutic approach for ischemic stroke, emphasizing the importance of targeting pyroptosis in stroke treatment.

The impact of white matter hyperintensities on short-term outcomes of reperfusion therapy in patients with acute ischemic stroke.

This study aimed to explore the impact of white matter hyperintensities (WMH) on the short-term outcomes of reperfusion therapy in acute ischemic stroke (AIS) patients. We prospectively collected data on AIS patients undergoing reperfusion therapies at Chengdu Second People's Hospital from January 2020 and January 2024. WMH severity was graded as 0-3 (none to moderate) or 4-6 (severe) by the Fazekas scale. We analyzed National Institutes of Health Stroke Scale (NIHSS) scores, good functional outcomes (modified Rankin Scale, mRS 0-2) at 7days and discharge, and safety outcomes like in-hospital mortality and intracranial hemorrhage. During the study period, 669 patients were included, with 345 having none to moderate WMH and 324 with severe WMH. Patients with severe WMH exhibited significantly higher NIHSS and mRS at 7days and discharge, with a decrease in good outcomes (mRS 0-2: 40.43% vs. 75.65%), and an increase in intracranial hemorrhage (16.4% vs. 5.8%) and in-hospital mortality (11.7% vs. 2.0%) compared with none to moderate WMH patients. After matching the baseline data, none to moderate WMH was associated with higher likelihood of good outcomes at discharge [adjusted odds ratio (aOR), 2.142; 95% confidence interval (CI), 1.380-3.304; P < 0.001] and a lower rate of any intracranial hemorrhage (aOR, 0.348; 95% CI 0.180-0.673; P < 0.001), with no significant difference in in-hospital mortality between the groups. Severe WMH could reduce the benefits of reperfusion therapy in AIS, with increased risk of hemorrhagic complications, warranting further research into treatment strategies for these patients.

The potential risk factors of postoperative cognitive dysfunction for endovascular therapy in acute ischemic stroke with general anesthesia.

Postoperative cognitive dysfunction (POCD) frequently occurs following endovascular therapy for acute ischemic stroke (AIS). Given the complexity of predicting AIS clinically, there is a pressing need to develop a preemptive prediction model and investigate the impact of anesthesia depth on AIS. A total of 333 patients diagnosed with AIS were included in the study, comprising individuals with non-POCD (n = 232) or POCD (n = 101). Univariate and multivariate logistic regression analyses were utilized to examine the independent risk factors associated with POCD. A calibration, decision curve analysis, and precision-recall curves were employed to assess the model's goodness of fit. Multivariate regression analysis identified two inflammatory indicators, high-sensitivity C reactive protein (hs-CRP) and systemic immune inflammatory index (SII), and three brain injury indicators, National Institute of Health Stroke Scale (NIHSS) score, N-terminal pro-brain natriuretic peptide (NT-proBNP), and soluble protein-100 β (S100-β), which were used to construct a nomogram model. The composite predictive model incorporating NIHSS score, hs-CRP, SII, NT-proBNP, and S100-β demonstrated efficacy in predicting POCD following AIS. Additionally, our results suggest a potential association between depth of anesthesia, cognitive impairment, and inflammatory response in AIS patients.

Secretome from hypoxic mesenchymal stem cells as a potential therapy for ischemic stroke: Investigations on VEGF and GFAP expression

Ischemic stroke is a sudden onset of neurological deficit resulting from a blockage in cerebral blood vessels, which can lead to brain tissue damage, chronic disability, and increased risk of mortality. Secretome from hypoxic mesenchymal stem cells (SH-MSC) is a potential therapy to improve neurological deficit by increasing the expression of vascular endothelial growth factor (VEGF) and reducing glial fibrillary acidic protein (GFAP). These effects can reduce the infarction area of ischemic stroke. Therefore, the aim of this study was to analyze the effect of 150 μL and 300 μL SH-MSC injection on VEGF and GFAP expression as well as the improvement of infarction area in ischemic stroke animal model. A post-test-only experimental design with consecutive sampling was used, with Rattus norvegicus as subjects. Stromal mesenchymal stem cells (S-MSCs) were isolated from the umbilical cords of rats at 21 days of gestation. Secretome production by the S-MSCs was induced under a hypoxic condition, and subsequently isolated. The resultant secretome was administered to rats subjected to middle cerebral artery occlusion (MCAO) at doses of 150 μL (P1 group) and 300 μL (P2 group). The results showed that the infarction area was reduced in P1 (p&lt;0.001) and P2 groups (p&lt;0.001). SH-MSC at a dose of 300 μL increased the expression of VEGF (p=0.028) and reduced the expression of GFAP (p=0.001). In conclusion, secretome from hypoxic S-MSC could potentially improve ischemic stroke by upregulating VEGF expression and downregulating GFAP expression.

Gut Microbiota, Bacterial Translocation, and Stroke: Current Knowledge and Future Directions.

Stroke is one of the most devastating pathologies in terms of mortality, cause of dementia, major adult disability, and socioeconomic burden worldwide. Despite its severity, treatment options remain limited, with no pharmacological therapies available for hemorrhagic stroke (HS) and only fibrinolytic therapy or mechanical thrombectomy for ischemic stroke (IS). In the pathophysiology of stroke, after the acute phase, many patients develop systemic immunosuppression, which, combined with neurological dysfunction and hospital management, leads to the onset of stroke-associated infections (SAIs). These infections worsen prognosis and increase mortality. Recent evidence, particularly from experimental studies, has highlighted alterations in the microbiota-gut-brain axis (MGBA) following stroke, which ultimately disrupts the gut flora and increases intestinal permeability. These changes can result in bacterial translocation (BT) from the gut to sterile organs, further contributing to the development of SAIs. Given the novelty and significance of these processes, especially the role of BT in the development of SAIs, this review summarizes the latest advances in understanding these phenomena and discusses potential therapeutic strategies to mitigate them, ultimately reducing post-stroke complications and improving treatment outcomes.

The realities of modern practice and prospects for the implementation of standards of secondary care for patients with acute stroke in the Left Bank of Kyiv Region according to the data of the hospital register (literature review and own research)

Background. The purpose of our work is to study the main indicators of the quality of care for patients with an acute stroke in individual hospitals of the Left Bank of the Kyiv Region of Ukraine. Materials and methods. The research was carried out at the Department of Nervous Diseases of the Shupyk National Healthcare University of Ukraine, on the basis of CNCE “Brovary Multidisciplinary Clinical Hospital”, angioneurological department with 85 beds (hereinafter — BMCH), and 4 secondary care centers with decentralized localization in the Kyiv Region (hereinafter — CDHKRLBU). The named departments are located 80–100 km, and BMCH is 15 km away from the regional center. They work according to an approved local protocol that meets industry standards for the management of patients with acute cerebral stroke and existing clinical guidelines. A total of 10,608 hospitalized patients with acute cerebral stroke were included in the prospective, cohort study (5,818 patients in BMCH and 4,790 patients in CDHKRLBU). For each case, the RES-Q (version 1.2) was filled out — a report form in an international program developed by the ESO-EAST initiative. Results. The study showed that the quality of care for stroke patients can be influenced by the material and technical base of the institution, as well as availability of diagnostic equipment, bed capacity and, of course, the logistical location, distance from the regional center. All quality indicators point to the leadership of BMCH compared to CDHKRLBU, and this has explanations. Conclusions. The study identified both positive and negative aspects of the therapeutic and diagnostic work in healthcare facilities, as well as factors influencing the success of treatment outcomes for patients with acute stroke. These findings have convincingly confirmed the relevance of studying quality care indicators and support the further implementation of the hospital registry method (based on RES-Q registry principles) in other areas of Kyiv Region and across Ukraine to evaluate and monitor the quality of medical care, including the analysis of the effectiveness of new technologies. During the study, BMCH purchased a new SCT, Philips Intera 1.5T MRI scanner (Netherlands), and Siemens angiograph in 2021, which improved the diagnosis of cerebral strokes and the use of treatment of thrombolytic therapy, thrombus extraction within the Left Bank of the Kyiv Region of Ukraine. Neighboring hospitals acquired SCT and expanded thrombolytic therapy for ischemic stroke. Of course, the research conducted is positive, because it becomes possible to identify certain shortcomings in the work and formulate recommendations for planning measures to improve medical care for stroke patients, as well as to compare the results of activities at the international and national levels.

Astragalus membranaceus-Carthamus tinctorius herb pair antagonizes parthanatos in cerebral ischemia/reperfusion injury via regulating PARP-1/TAX1BP1-mediated mitochondrial respiratory chain complex I.

The combination of Astragalus membranaceus (Huang Qi in Chinese, HQ) and Carthamus tinctorius (Hong Hua in Chinese, HH) is commonly employed for treating ischemic stroke (IS). The heavily oxidative environment of cerebral ischemia/reperfusion injury (CI/RI) promotes activation of poly (ADP-ribose) polymerase-1 (PARP-1), which initiates parthanatos, a regulated cell death mode. Reactive oxygen species (ROS) bursting in mitochondrial respiratory chain complex I (Complex I) is a key cause of CI/RI. Nevertheless, the intrinsic mechanism of its involvement in Complex I in the parthanatos cascade remains obscure. This experiment aimed to investigate that HQ-HH antagonized parthanatos via regulating PARP-1/TAX1BP1-mediated Complex I to attenuate CI/RI. The HPLC fingerprint of HQ-HH was established, and the contents of 9 components were determined. The neuroprotective effect of HQ-HH in CI/RI was evaluated by rat middle cerebral artery occlusion/reperfusion (MCAO/R) and BV2 cell oxygen glucose deprivation/reoxygenation (OGD/R) models. Pathological changes in brain tissue of MCAO/R rats were observed using TTC staining, HE staining, and TEM. Complex I activity was measured in MCAO/R rats and OGD/R-treated BV2 cells. qRT-PCR and Western blot were performed to detect the expressions of related genes and proteins of parthanatos and Complex I as well as tax1 binding protein 1 (TAX1BP1). Immunofluorescence staining was employed to certify the nuclear translocation of apoptosis-inducing factor (AIF) in MCAO/R rats. The HPLC fingerprint of HQ-HH with 25 common peaks and the contents of 9 components were obtained. HQ-HH improved behavioral function and alleviated cerebral infarction in MCAO/R rats in a dose-dependent manner. HQ-HH alleviated parthanatos and exhibited the same repressive effect on PARP-1 transcription and translation as PJ34 (PARP-1 inhibitor). Moreover, the migration of TAX1BP1 to the mitochondria was restrained with HQ-HH treatment as a downstream of PARP-1, resulting in the inhibition of Complex I activity and less ROS production, accompanied by a decrease in mRNA and protein levels of ND1 and ND2. Subsequently, the nuclear translocation of AIF and the generation of poly(ADP-ribose) (PAR) polymers were suppressed. HQ-HH mitigated CI/RI by regulating PARP-1/ TAX1BP1 to inhibit the Complex I activity with less ROS production, further impeding nuclear translocation of AIF, and ultimately antagonizing parthanatos. By emphasizing the link between parthanatos and Complex I, we anticipate providing new empirical evidence for HQ-HH therapy of IS.

ROS-responsive quercetin-based polydopamine nanoparticles for targeting ischemic stroke by attenuating oxidative stress and neuroinflammation.

Ischemic stroke (IS), a prevalent cerebrovascular disorder, is characterized by high morbidity rates and significant disability. However, relevant drug therapy for IS still suffers from limitations such as limited blood-brain barrier (BBB) penetration efficiency, single therapeutic target, short half-life, and strong side effects. The development of multi-target neuroprotective agents using natural drug molecules with low toxicity and combining them with nanotechnology to improve BBB permeability and drug utilization is an important direction in the development of IS therapeutic strategies. Based on the anti-inflammatory and antioxidant properties of quercetin (Que), as well as the ROS-responsive degradation properties of polydopamine (PDA), an IS therapeutic strategy (Que@DAR NPs) was developed in this study. Que@DAR NPs were formed by dopamine wrapping Que by oxidative self-assembly and wrapping the rabies virus glycoprotein (RVG29) on the surface. The results showed that Que@DAR NPs greatly improved the dispersion stability of Que and exhibited ROS-responsive degradation properties. Cellular internalization assay in human neuroblastoma cells (SH-SY5Y) showed that RVG29 peptide substantially augmented the cellular uptake of Que@DAR NPs. Moreover, Que@DAR NPs can effectively reduce the oxidative damage of SH-SY5Y cells and induce the polarization of microglia to anti-inflammatory (M2) phenotype. In vivo studies further demonstrated that Que@DAR NPs inhibited neuroinflammation, reduced neuronal apoptosis, and significantly ameliorated neurological dysfunction in a rat model of middle cerebral artery occlusion (MCAO). In conclusion, Que@DAR NPs provide a safe and effective new strategy for the precision treatment of IS.

Medical management versus intravenous thrombolysis for patients with minor non-disabling acute ischemic stroke: A systematic review and meta-analysis

Background: The efficacy and safety of thrombolysis therapy in patients with mild stroke, especially acute non-disabling stroke is controversial. We intend to conduct this systematic review and meta- analysis to evaluate the efficacy and safety of thrombolytic therapy compared to medical management in acute non-disabling stroke. Methods: We searched multiple databases to obtain articles related to medical management and intravenous thrombolysis therapy for minor non-disabling acute ischemic stroke from inception until November 28, 2023, and the search was conducted again on September 1, 2024. The primary outcome was functional independence (modified Rankin scale [mRS] score of 0 to 2) at 90 days. All analyses were performed using the random effect model. The quality of articles was evaluated through the Cochrane risk assessment tool and Newcastle-Ottawa scale. Results: 2 RCTs and 7 cohort studies met the inclusion criteria. The merge analysis showed that there was no significant difference in improving functional independence (mRS 0-2, RR: 1.01, 95% CI 0.98 - 1.04, P = 0.47) and excellent outcome (mRS 0-1) of patients with minor non-disabling acute ischemic stroke between IVT and medical management. However, IVT would increase the risk of early neurological deterioration (RR: 0.50, 95% CI 0.30 - 0.82, P = 0.007), compared to medical management. Analysis of the cohort studies showed that there was a significant correlation between IVT and sICH (RR: 0.20, 95% CI: 0.06 - 0.68, P=0.01). Conclusions: For patients with minor non-disabling acute ischemic stroke, medical management will not have a negative impact on functional recovery, and may be a safer alternative.