Search Results (262)

Ischemic stroke is a primary cause of cerebrovascular diseases and continues to be one of the leading causes of death and disability among patients worldwide. Pathological processes caused by vascular damage due to stroke occur in a time-dependent manner and are classified into three categories: acute, subacute, and chronic. Current treatments for ischemic stroke are limited to effectiveness in the early stages. In this study, we investigated the therapeutic effect of an oriental medicine, Gosha-jinki-gan (TJ107), on improving chronic ischemic stroke using the mouse model with middle cerebral artery occlusion (MCAO). The changes in the intracerebral inflammatory response (macrophages (F4/80), TLR2•4, IL-23, IL-17, TNF-α, and IL-1β) were examined using real-time RT-PCR. The MCAO mice showed the increased expression of glial fibrillary acidic protein (GFAP) and of F4/80, TLR2, TLR4, IL-1β, TNF-α, and IL-17 in the brain tissue from the MCAO region. This suggests that they contribute to the expansion of the ischemic stroke infarct area and to the worsening of the neurological symptoms of the MCAO mice in the chronic phase. On the other hand, the administration of TJ107 was proven to reduce the infarct area, with decreased GFAP expression, suppressed macrophage infiltration in the brain, and reduced TNF-α, IL-1β, and IL-17 production compared with the MCAO mice. This study first demonstrated Gosha-jinki-gan’s therapeutic effects on the chronic ischemic stroke. Full article

Early rehabilitation is essential for restoring functional recovery in patients with stroke, particularly during the early phase of post-acute care (PAC), or the subacute stage. We aimed to evaluate the effectiveness of a 7-week PAC rehabilitation program in improving muscle strength, physical performance, and functional recovery. A total of 219 inpatients with stroke in the subacute stage were initially recruited from the PAC ward of a regional teaching hospital in Northern Taiwan, with 79 eligible patients—within 1 month of an acute stroke—included in the analysis. The program was delivered 5 days per week, with 3–4 sessions daily (20–30 min each, up to 120 min daily), comprising physical, occupational, and speech–language therapies. Sociodemographic data, muscle strength, physical performance (Berg Balance Scale [BBS], gait speed, and 6-minute walk test [6MWT]), and functional recovery (modified Rankin Scale [mRS], Barthel Index [BI], Instrumental Activities of Daily Living [IADL], and Fugl–Meyer assessment: sensory and upper extremity) were collected at baseline, 3 weeks, and 7 weeks. Generalized estimating equations analyzed program effectiveness. Among the 56 patients (70.9%) who completed the program, significant improvements were observed in the muscle strength of both the affected upper (B = 0.93, p < 0.001) and lower limbs (B = 0.88, p < 0.001), as well as in their corresponding unaffected limbs; in physical performance, including balance (BBS score: B = 9.70, p = 0.003) and gait speed (B = 0.23, p = 0.024); and in functional recovery, including BI (B = 19.5, p < 0.001), IADL (B = 1.48, p < 0.001), and mRS (B = −0.13, p = 0.028). These findings highlight the 7-week PAC rehabilitation program as an effective strategy during the critical recovery phase for patients with stroke. Full article

Astrocyte activation and gender differences play critical roles in the prognosis following stroke. Recent studies have shown that optogenetic technology can promote brain repair after stroke by activating astrocytes in male rats. However, it remains unclear whether gender differences influence the efficacy of optogenetic activation of astrocytes in regulating post-stroke brain repair and its underlying mechanisms. In this study, we activated astrocytes in the ipsilateral cortex of adult glial fibrillary acidic protein-channelrhodopsin 2-enhanced yellow fluorescent protein (GFAP-ChR2-EYFP) transgenic Sprague Dawley rats using optogenetic stimulation at 24, 36, 48, and 60 h after inducing photothrombosis stroke. Neurobehavioral tests, cresyl violet staining, RT-qPCR, Western blot, and immunofluorescence analysis were performed on both female and male rats. Our results showed that male rats exhibited significant improvements in behavioral scores and reduction in infarct size after optogenetic activation of astrocytes at three days post-stroke (p < 0.05), whereas no significant changes were observed in female rats. Additionally, in female rats, the expression of basic fibroblast growth factor (bFGF) increased after ischemic stroke and astrocytic optogenetic stimulation (p < 0.05), leading to enhanced endothelial cell proliferation compared to male rats (p < 0.05). In vitro experiments further demonstrated that the astrocyte activation was inhibited in the presence of bFGF (p < 0.05). These findings suggest that the increase in bFGF levels in females following stroke may inhibit the optogenetic activation of astrocytes, thereby attenuating the therapeutic effect of astrocyte activation on post-stroke brain repair. This study provides important insights into the gender-specific roles of astrocytes in the acute phase of ischemic stroke. Full article

Background/Objectives: Immature platelet fraction (IPF) and reticulated platelets (RPs) are biomarkers reflecting the youngest and most metabolically active platelets in circulation. RPs, a subset of immature platelets, contain residual RNA and have been associated with increased thrombotic potential. Elevated IPF levels indicate enhanced platelet production, commonly observed during elevated platelet turnover, such as in autoimmune reactions, consumption, and thrombotic events. This systematic review aims to evaluate the potential role of IPF and RPs in the context of cerebrovascular events, specifically ischemic and hemorrhagic stroke, as well as transient ischemic attacks (TIAs), and to assess their clinical utility in stroke monitoring and management. Methods: A comprehensive literature search was conducted in PubMed, Scopus, Cochrane Library, and Web of Science for studies published between 2000 and 2024, which focused on IPF and RPs in human subjects with cerebrovascular events. Results: Six studies met the inclusion criteria. Findings suggest that elevated levels of IPF and RP are associated with the acute and chronic phases of ischemic stroke and TIA and may reflect increased platelet turnover and thrombotic activity. Some evidence supports their role in predicting stroke severity, recurrence, and underlying etiology, although results are not yet consistent across all studies. Conclusions: IPF and RPs are emerging biomarkers with potential applications in acute ischemic stroke and risk stratification. While current evidence is promising, further research is needed to standardize measurement techniques and validate their routine use in clinical practice. Full article

The insulin-like growth factor (IGF) system has significance for poststroke outcomes. Previously, we reported that low serum IGF-II (s-IGF-II) in the acute phase is associated with poststroke mortality, and that IGF-II is lower among males. Given the known interactions of the IGF system and estrogen receptor signaling, s-IGF-II may have sex-specific effects. In this study, we conducted a secondary analysis of sex differences in s-IGF-II and poststroke functional outcomes and mortality after ischemic stroke (IS) in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS, males; n = 315, females; n = 177). Functional outcomes were assessed using the modified Rankin scale (mRS) at 3 months and 2 years poststroke. Survival was recorded for 7 years or until death. Males in the lowest quintile of acute s-IGF-II had a higher poststroke mortality, with a crude hazard ratio [HR] of 2.52 (95% confidence interval [CI]) 1.59–3.99) and an adjusted HR of 1.83 (95% CI 1.09–3.06). No corresponding significant association was observed in females. Although acute s-IGF-II was crudely associated with poor functional outcomes among males after 3 months and 2 years, these associations were not independent of initial stroke severity in adjusted models. In conclusion, low levels of acute s-IGF-II are linked with poststroke mortality among males, but not significantly in females. Further studies are, however, warranted with sex hormone analysis, consideration of specific cause of death, and more females. Full article

Ischemic stroke (IS) is the leading cause of disability and death worldwide, and its high incidence, disability and recurrence rates impose a heavy economic burden on families and society. Recent studies have shown that oxidative stress plays a key role in the pathophysiological mechanisms of ischemic stroke, not only participating in the onset and development of neuronal damage in the acute phase but also significantly influencing the long-term prognosis of ischemic stroke through molecular mechanisms, such as epigenetic modifications. However, the potential targets of oxidative stress-related genes in IS and their mechanisms of action remain to be elucidated. The aim of this study was to systematically analyse the function and significance of oxidative stress-related genes in IS. We obtained IS-related gene expression datasets from the GEO database and integrated known oxidative stress-related genes from the Genecards database for cross-analysis. Multidimensional feature screening using unsupervised consensus clustering and a series of machine learning algorithms led to the identification of the signature gene GPX7. The correlation between this gene and immune cell infiltration was assessed using MCPcounter and a potential therapeutic agent, glutathione, was identified. Binding was verified by molecular docking (MD) analysis. In addition, single-cell RNA sequencing data were analysed to further reveal expression in different cell types and its biological significance. Finally, we performed in vivo experiments using the Wistar rat middle cerebral artery occlusion (MCAO) model, and the results indicated that GPX7 plays a key role in IS, providing a new theoretical basis and potential intervention target for the precise treatment of IS. Full article

Background and aims: Recent advances in acute stroke interventions have highlighted the importance of accurate determination of infarct volume in the evaluation of acute stroke patients, carrying important prognostic and therapeutic implications for treatment planning, outcome prediction, and evaluation of the success of therapeutic interventions. However, there is no consensus on the methodologies employed to measure cerebral infarct volume. We aimed to assess the reproducibility and reliability of methods employed in the clinical determination of infarct volume in acute ischaemic stroke. Methods: We carried out a systematic review of studies assessing methodologies for the determination of infarct volume in the acute phase (<24 h). We searched Medline PubMed, Scopus, Cinahl, Cochrane Library, Web of Science, and Embase for studies examining image-based diagnosis of acute ischaemic stroke < 24 h by CT or MRI. Data on patient cohorts, imaging type, time from symptoms onset, methodologies and quantification strategies, rater reliability, accuracy, sensitivity, and specificity were compared. Results: We identified eighteen eligible studies with a total of 3298 ischaemic stroke patients assessing a variety of manual, semi-automated, and fully-automated methods. The ABC/2 method was found to be highly reliable, reproducible, and accurate, and provides the best manual estimate of infarction, but has a tendency to under- or overestimate infarct volume. Semi-automated and automated approaches with user refinement showed excellent inter-rater and intra-rater correlation. However, differences in operating algorithms and lack of standardisation of image acquisition parameters, quality, and format may impact performance and reproducibility. Conclusions: Of all methods, automated and semi-automated approaches utilising rater judgment and refinement represent the most robust approaches, with semi-automated tools demonstrating consistent and repeatable results. We recommend a standardised reporting of study methodologies for the accurate interpretation and comparison of efficacy of therapeutic interventions and patient outcomes, especially in a multi-centre setting. This may allow for more effective evaluation of stroke therapies and accelerate ischaemic stroke treatment decisions. Full article

Background and Purpose: Accurate and reproducible methods for assessing infarct volume in acute ischaemic stroke have important therapeutic and prognostic implications for the choice and success of acute therapeutic interventions. However, there is no international consensus on the methodology employed in infarct volume assessment. We aimed to assess the reliability of the ABC/2 score and e-ASPECTS in the determination of infarct volume in acute ischaemic stroke. Methods: Infarct volume was measured from NCCT in stroke patients recruited ≤12 h of symptoms onset and at 24 h using the ABC/2 method. Automated ischaemic volume measurements were carried out using e-ASPECTS software. Measurements using ABC/2 were compared with e-ASPECTS to assess volume differences and reliability using Lin’s concordance correlation coefficient. Results: Thirty-three patients with CT < 12 h from onset of symptoms and follow-up at 24 h were included in the analysis. Use of ABC/2 demonstrated low agreement between observers (0.490, CI 0.236–0.743, p < 0.001) on admission (<12 h). High agreement was found between observers at 24 h (0.724, CI 0.564–0.884, p < 0.001). High agreement was observed between the mean observed infarct volumes using ABC/2 and e-ASPECTS on admission (0.794, CI 0.691–0.898, p < 0.001). Conclusions: Our results suggest that e-ASPECTS is a reliable platform for ischaemic volume determination particularly in the hyperacute phase to inform management. However, the use of ABC/2 represents an alternative approach to e-ASPECTS in the rapid and reliable estimation of ischaemic infarct volume to inform prognosis and treatment decisions, particularly in cases of delayed presentation where infarction is established and arterial territory boundaries are easily identifiable. Full article

Background and Objectives: Thermography is a non-invasive diagnostic technique that measures skin surface temperatures to reflect normal or abnormal physiology. This review explores the clinical utility of thermography in diagnosing and monitoring stroke, with an emphasis on its clinical applications. Materials and Methods: This systematic review followed PRISMA guidelines, with a protocol published prior to analysis. Three databases were screened up to end of 2024. Article selection was conducted in two stages: title and abstract screening using Rayyan^®, followed by full-text eligibility assessment. Discrepancies were resolved through consensus. Risk of bias assessment was performed with ROBINS-I. Narrative synthesis was planned in addition to descriptive statistics. Results: A total of 20 studies were included after screening 277 records. Thermography emerged as a promising tool for stroke patients in both the acute and chronic phases. In the acute phase, it demonstrated potential in detecting early signs of carotid occlusive disease by identifying temperature differences in the forehead or neck regions. Additionally, thermography contributed to the differential diagnosis of Wallenberg syndrome. In the chronic phase, it exhibited clinical utility in monitoring rehabilitation progress. Conclusions: Thermography shows promise as a non-invasive tool for stroke assessment and monitoring. While preliminary studies suggest physiological relevance, its clinical utility remains investigational and requires further validation. Full article

The Coronavirus Disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), disproportionately affects individuals with diabetes mellitus (DM) by exacerbating cardiovascular and renal complications. This increased risk is mediated through immune dysfunction, chronic inflammation, hyperglycemia, dysregulation of renin-angiotensin system dysregulation, endothelial dysfunction, and hypercoagulability. Epidemiological studies indicate a two-fold increased risk of stroke and end-stage renal disease in SARS-CoV-2-infected individuals with diabetes, along with a 60% higher risk of cardiovascular disease. While antidiabetic therapies like sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists show potential protective effects, insulin use in hospitalized patients is linked to higher mortality. Vaccination is crucial in reducing severe COVID-19 outcomes and mitigating post-infection complications, including new-onset diabetes. While concerns exist regarding vaccine-associated nephropathy and thromboembolic events, these risks are thought to be minimal compared to the benefits. As COVID-19 shifts to an endemic phase, the long-term renal and cardiovascular outcomes in patients with DM remain uncertain, highlighting the urgent need for continued research and targeted management strategies. Full article

Objective: The contralateral hippocampus, a critical region for cognitive function, is often overlooked in everyday clinical practice and stroke research. This study aimed to evaluate the effect of specific antiplatelet agents on the hippocampus (ipsilateral and contralateral) during the hyperacute phase of stroke. Materials and Methods: Twelve-week-old rats were randomly assigned to four groups, each containing six rats: a cilostazol group, an aspirin group, an aspirin plus cilostazol group, and a control group. Each substance was administered for four weeks. Permanent brain ischemia was induced over 2 h using intraluminal middle cerebral artery occlusion. A neurologic examination was conducted, followed by euthanasia and histological examination of the CA1 hippocampal region. The hematoxylin and eosin stain was used to assess the total number of intact neuronal cell bodies and pyknotic nuclei, an indicator of early irreversible neuronal injury. Results: In the ipsilateral hippocampus, monotherapy with either aspirin or cilostazol significantly reduced pyknotic nuclei compared with the control group (p = 0.0016 and p = 0.0165, respectively). However, combination therapy showed no significant difference from the controls (p = 0.2375). In the contralateral hippocampus, cilostazol monotherapy demonstrated significantly reduced pyknotic nuclei (p = 0.0098), whereas aspirin monotherapy and combination therapy did not (p = 0.1009 and p = 0.9999, respectively). A cumulative analysis of both hemispheres revealed that monotherapy with aspirin or cilostazol markedly reduced injury markers (p = 0.0002 and p = 0.0001, respectively), whereas combined therapy revealed no significant benefit (p = 0.1984). A neurological assessment indicated that the most severe deficits were in the combination therapy group. Conclusions: To the best of our knowledge, this is the first study to compare acute histopathological changes in the affected and unaffected hippocampus after a stroke in a rat model. Dual antiplatelet therapy resulted in worse outcomes (histopathological and neurological) than monotherapy. Full article

Background: Models of second-phase cardiac rehabilitation (CR) following myocardial infarction (MI) differ across countries. The aim of this study was to compare outcomes in MI survivors participating in outpatient and inpatient CR programs. Methods: All patients hospitalized for acute MI in Poland between October 2017 and December 2018 (n = 96,634) were included in the study. Among them, 4411 patients were referred to and commenced outpatient CR, whereas 11,626 patients started inpatient CR within 30 days following discharge. Results: The mean follow-up period was 332.8 ± 128.1 days. Younger age, male sex, and a history of cancer were associated with a higher probability of participating in outpatient CR, whereas diabetes, heart failure, chronic kidney disease, chronic obstructive pulmonary disease, ST-elevation MI, and myocardial revascularization were associated with a lower likelihood of outpatient CR participation. Participation in outpatient CR was linked to a reduced risk of all-cause mortality, in both univariable (hazard ratio [95% confidence interval]: 0.37 [0.26–0.51]) and multivariable analyses (0.53 [0.38–0.74]). Outpatient CR was also associated with a lower risk of death, MI, or stroke (0.57 [0.48–0.67] in univariable analysis and 0.72 [0.61–0.84] in multivariable analysis), as well as a lower risk of death or cardiovascular hospitalization (0.78 [0.73–0.84] and 0.85 [0.80–0.91], respectively). Conclusions: Outpatient CR following MI tends to occur alongside a better prognosis compared to inpatient programs. Full article

Background: Endovascular mechanical thrombectomy (EVT) is regarded as the standard treatment for acute ischemic stroke with large vessel occlusion. Few studies have examined the evolution of cerebral flow after the acute stage of ischemic stroke. In this study, we examined the association of functional outcomes with cerebral blood flow by extracranial carotid sonography during the subacute phase after EVT and multiple prognostic variables. Methods: We conducted a single-center, retrospective, observational study between January 2018 and June 2023. Patients with acute stroke resulting from anterior circulation large vessel occlusion who underwent EVT were included. All patients underwent carotid sonography in the second week after EVT. Patients with fair (modified Rankin Scale [mRS]: 0–3) and poor outcomes (mRS: 4–6) were compared to determine the association between and identify the predictors of these factors and functional outcomes. Results: A total of 89 patients were included (female: 38 (42.7%); mean age: 69.45 ± 13.59 years). Multivariable logistic regression analysis revealed that three factors were independent predictors of fair outcomes: (1) the Alberta Stroke Program Early CT Score (odds ratio [OR]: 1.79; 95% confidence interval [CI]: 1.16–2.78; p = 0.009); (2) Thrombolysis in Cerebral Infarction 2b to 3 (OR: 4.91; 95%CI: 1.10–21.89; p = 0.037); (3) the ratio of treatment-side blood flow between the internal carotid artery and common carotid artery (QTI/QTC, OR: 45.35; 95% CI: 1.11–1847.51; p = 0.04). Conclusions: The ratio of QTI/QTC is a clinically relevant parameter as a potential predictor of favorable outcomes. This parameter can be used to formulate patient prognostic scores and help clinicians determine whether adequate cerebral perfusion is maintained during the subacute phase. Full article

Ischemic stroke is a leading cause of death and disability worldwide. Currently, there is an unmet clinical need for pharmacological treatments that can improve ischemic stroke outcomes. In this study, we investigated the role of brain peroxisome proliferator-activated receptor alpha (PPARα) in ischemic stroke pathophysiology. We used a well-established model of cerebral ischemia in PPARα transgenic mice and conducted the RNA sequencing (RNA-seq) of mouse stroke brains harvested 48 h post-middle cerebral artery occlusion (MCAO). PPARα knockout (KO) increased brain infarct size following stroke, indicating a protective role of PPARα in brain ischemia. Our RNA-seq analysis showed that PPARα KO altered the expression of genes in mouse brains with known roles in ischemic stroke pathophysiology. We also identified many other differentially expressed genes (DEGs) upon the loss of PPARα that correlated with increased infarct size in our stroke model. Gene set enrichment analysis (GSEA) and Gene Ontology (GO) analysis revealed the upregulation of gene signatures for the positive regulation of leukocyte proliferation, apoptotic processes, acute-phase response, and cellular component disassembly in mouse stroke brains with PPARα KO. In addition, pathway analysis of our RNA-seq data revealed that TNFα signaling, IL6/STAT3 signaling, and epithelial–mesenchymal transition (EMT) gene signatures were increased in PPARα KO stroke brains. Our study highlights PPARα as an attractive drug target for ischemic stroke due to its transcriptional regulation of inflammation-, apoptosis-, and EMT-related genes in brain tissue following ischemia. Full article

Background and Clinical Significance: The pathogenesis of ischemic lesions in tubercular meningoencephalitis remains unclear, as do the best therapeutic strategies during the acute phase and for secondary prevention. Case Presentation: We report on an atypical case of tubercular meningoencephalitis with a concomitant ischemic stroke. The infectious origin of the ischemic lesion was hypothesized due to a discrepancy between clinical and radiological findings. The patient underwent neuroimaging, blood tests, and a lumbar puncture to diagnose tubercular meningoencephalitis. She subsequently started on antitubercular therapy. Despite the initiation of treatment, her neurological condition worsened. A computed tomography revealed hydrocephalus, leading to the placement of an external ventricular shunt. This intervention resulted in a reduction in ventricular size and an overall improvement in her clinical condition. To reduce the risk of death, secondary prophylaxis with cardioaspirin was added to her treatment regimen. Conclusions: This report highlights the diagnostic and therapeutic challenges encountered in managing patients with tubercular meningitis presenting with concomitant ischemic stroke. By elucidating the complexities of this clinical scenario, we emphasize the importance of early recognition, comprehensive evaluation, and multidisciplinary management to optimize patient outcomes. Full article