Hemorrhagic Stroke Research Articles

GSTO2 ameliorates human neuroblastoma cell apoptosis, inflammation, ferroptosis, and oxidative stress by upregulating GPX4 expression in intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a severe hemorrhagic stroke and induces severe secondary neurological injury. However, its pathogenesis remains to be explored. The present work investigates the role of glutathione S-transferase omega 2 (GSTO2) in ICH and the underlying mechanism. Human neuroblastoma cells (SK-N-SH) were stimulated using hemin to mimic ICH-like injury. Protein expression levels of GSTO2 and glutathione peroxidase 4 (GPX4) were detected by western blot analysis assay. Cell viability was assessed by cell counting kit-8 assay. Cell proliferation was investigated by 5-ethynyl-2'-deoxyuridine assay. Cell apoptosis was analyzed by flow cytometry. Interleukin-6 and tumor necrosis factor-α levels were quantified by enzyme-linked immunosorbent assays. Fe2+ colorimetric assay kit was used to detect Fe2+ level. A cellular reactive oxygen species (ROS) assay kit was used to detect ROS levels. Malondialdehyde (MDA) level was assessed using the MDA content assay kit. GSH level was quantified using the GSH assay kit. Co-immunoprecipitation assay was performed to identify the association between GSTO2 and GPX4. Hemin stimulation suppressed SK-N-SH cell proliferation and promoted cell apoptosis, cell inflammation, ferroptosis, and oxidative stress. GSTO2 expression was downregulated in hemin-treated SK-N-SH cells in comparison with the control group. In addition, ectopic GSTO2 expression counteracted hemin-induced inhibitory effect on cell proliferation and promoting effects on cell apoptosis, inflammation, ferroptosis, and oxidative stress. Moreover, GSTO2 was associated with GPX4 in SK-N-SH cells. GPX4 silencing attenuated GSTO2 overexpression-induced effects on hemin-stimulated SK-N-SH cell injury. GSTO2 ameliorated SK-N-SH cell apoptosis, inflammation, ferroptosis, and oxidative stress by upregulating GPX4 expression in ICH, providing a therapeutic strategy for ICH.

ИНСУЛЬТ МЕНЕН ООРУГАН БЕЙТАПТАРДАГЫ ТЕРЕҢ ТАМЫР ТРОМБОЗУНУН ТОБОКЕЛДИК ФАКТОРЛОРУ ЖАНА БОЖОМОЛДООЛОРУ (ИЛИМИЙ АДАБИЯТТАРДЫ КАРАП ЧЫГУУ)

Currently there is no reliable evaluation system for predicting deep vein thrombosis (DVT) in the hospital after ischemic and even more – hemorrhagic stroke. Objective: to review current literature data on the verification of risk factors for the development of DVT in stroke patients and aggressive and early screening strategies in the early post-stroke period. Three fundamental factors underlie the development of DVT: damage to the venous wall, the tendency of blood to hypercoagulation and slow blood flow. Most of the factors that are more or less associated with the development of thromboembolic events revolve around these 3 elements. Typical factors were older age, female gender, changes in the levels of clinical and laboratory variables such as D-dimer or scores on the Berg equilibrium scale. An effective model of risk stratification for DVT at the hospital level after a stroke would be useful for identifying high-risk patients and for implementing individual preventive strategies, therefore further population studies are needed, including in Kyrgyzstan.

A Prospective and Observational Study on the Impact of Patient Counselling on Medication Adherence and Quality of Life in Stroke Patients

PURPOSE: The study goals are to improve medication adherence and high-quality lifestyles in stroke patients through effective patient counselling. BACKGROUND: Stroke is one of the most common neurological disorders and the second most common purpose of dying worldwide. Stroke is likewise called cerebral infarction or cerebrovascular twist of fate. It occurs when blood flow to the brain is reduced due to permanent or temporary blockage of an artery that carries blood to the brain, or rupture of an artery in the brain because of high blood pressure The primary danger elements of Stroke encountered are high blood pressure, age, diabetes mellitus, obesity, smoking, and alcohol. the burden of stroke is gigantic and recurrence of stroke is a first-rate risk issue for growing the weight of stroke. medications play an crucial position in stopping stroke recurrence. Adherence can be summarized as ‘The extent to which someone’s behaviour taking medicinal drug, following a diet, and/or executing life-style modifications – corresponds with agreed tips from a health care provider”. current estimates are that only one-sixth of all sufferers come close to perfect adherence to their medicine regimen. the issue is gaining importance because of an increase in the prevalence of chronic diseases and an ageing population. common reasons of medicine nonadherence include complicated remedy regimens and patients’ lack of belief within the treatment. Healthcare specialists play an crucial position in remedy adherence amongst stroke survivors. They should deal with the boundaries and facilitate remedy adherence behaviours. METHODOLOGY: It is a prospective observational study conducted in Lalitha Super specialities Hospital, Guntur over 6 months duration study in the neurology department, a total of 200 patients of age groups between 25-85 of both genders with comorbidities like hypertension, diabetes, and affected with stroke were enrolled in the study. RESULTS & DISCUSSIONS: The outcomes were obtained after 6 months duration observe within the neurology branch of tertiary care hospital a total of 200 patients enrolled in the study. The study of the effect of patient counselling on medication adherence and quality of life in stroke patients is a prospective observational take a look at in which facts is amassed in Lalitha super speciality hospital with a random representative sampling method explaining the qualitative & quantitative evaluation. We accrued 200 instances of these tormented by ischemic, hemorrhagic, and transient ischemic stroke, and affected person counselling was given and followed up after discharge. Out of 2 hundred samples, 67% of patients are suffering from ischemic stroke, 22.5% from hemorrhagic & 10.5% from TIA. males (60.5%) are greater stricken by stroke than females (39.5%) and the age group between 46-55 is more affected by stroke (32%). The patients who are with both hypertension and diabetes were extra affected by stroke (45.5%) than the ones having single co-morbidities, high blood pressure (28%) and DM (13.5%). in the collected samples males are more effecting by hypertension (33.88%) and females with diabetes (15.18%) and both high blood pressure & diabetes (49.36%). medication adherence in stroke patients is the primary goal of the observe, figure no 5 indicates that out of 200 sufferers, 129 (sixty four.5%) have highly adhered to medicine, 61 patients (30.5%) are mild, and, 10 patients (5.0%) low adherence to remedy after counselling to the patients. quality of lifestyles is the main objective of this study. figure no 6 suggests the quality of life of 200 stroke patients earlier than and after patient counselling. The exceptional of lifestyles had been measured using a modified ranking SCALE (mRS). After the 6-month observe up the quality of life had improved in patients. A quantitative analysis was done using the chi-square test the end result of x squared value is 35.1 with Df 6 at a significance level of 0.05, and the P value is <0.05. CONCLUSION: The main aim of this study is to provide better patient counselling to improve medication adherence and the quality of life in stroke patients was achieved successfully. In this study 200 stroke patients were enrolled and patient counseling was provided and followed up through face-to-face interviews and phone calls. Among 200 patients, 129 patients (64.5%) were highly adherence to the medication and 61 patients (30.50%) were moderately. 10 patients (5%) were low adherence to medication. The quality of life of stroke patients increased after the counselling compared to before counselling. The medication adherence and quality of life were measured using MMAS-8 QUESTIONS and a modified ranking scale (mRS) respectively. It is also evident from the study that pharmacist intervention is effective in improving medication adherence and its associated effect on the management of patients receiving stroke therapy.

Motor and Cognitive Function Impairment as a Result of Haemorrhagic Stroke in a Hypertensive Patient: A Case Study

Stroke is a serious cerebrovascular disease that can cause disability and death if not diagnosed and treated early. Stroke is the leading cause of death among neurological diseases. In this case study, we describe the therapeutic history of decompression surgery in a 72-year-old patient with motor and cognitive function deficits after acute ischaemic stroke.

The combined impact of migraine and gestational diabetes on long-term risk of premature myocardial infarction and stroke: A population-based cohort study.

To examine the combined impact of migraine and gestational diabetes mellitus (GDM) on the risks of premature (persons aged ≤60 years) major adverse cardiovascular and cerebrovascular events (MACCE) based on a composite endpoint of fatal and non-fatal myocardial infarction (MI) and stroke. Migraine and GDM are risk factors for cardiovascular disease. It is unknown how the combination of migraine and GDM may affect cardiovascular disease risk. In a Danish population-based cohort longitudinal study, we established four cohorts among women with at least one pregnancy during 1996-2018: women with migraine, women with GDM, women with both migraine and GDM, and women free of migraine and free of GDM. Risks of premature MACCE and component endpoints were assessed for each cohort. We included 1,307,456 women free of migraine and free of GDM, 56,811 women with migraine, 24,700 women with GDM, and 1484 women with migraine and GDM. The 20-year absolute risk of MACCE was 1.3% (MI: 0.4%, ischemic stroke: 0.6%, hemorrhagic stroke: 0.3%) among women free of migraine and free of GDM, 2.3% (MI: 0.8%, ischemic stroke: 1.2%, hemorrhagic stroke: 0.5%) among women with migraine, 2.2% (MI: 1.0%, ischemic stroke: 1.0%, hemorrhagic stroke: 0.4%) among women with GDM, and 3.7% (MI: 1.7%, ischemic stroke: 1.7%, hemorrhagic stroke: 0.3%) among women with both migraine and GDM. The 20-year adjusted hazard ratio of premature MACCE was 1.65 (95% confidence interval [CI] 1.49-1.82) for women with migraine; 1.64 (95% CI 1.37-1.96) for women with GDM; and 2.35 (95% CI 1.03-5.36) for women with both GDM and migraine when compared with women free of migraine and free of GDM. Migraine and GDM were each independently associated with an increased risk of MACCE. Risk of premature MACCE was greatest among women with both migraine and GDM, although this risk estimate was imprecise.

Sex Difference in Disease-Related Adverse Events Post-Diagnosis of Lung Cancer Brain Metastases in Medicare Individuals ≥ 66 Years of Age.

Sex differences are evident in adverse events (AEs) related to brain tumors, yet sex differences in AEs specific to brain metastases (BrMs) are underexplored. Lung cancer BrMs dominate among BrM, comprising over half of cases. This study examined sex differences in AEs associated with lung cancer BrMs in individuals aged 66 or older using the SEER-Medicare dataset. Multivariable logistic regression, adjusted for demographic factors and comorbidities, stratified by histological subtype, treatment, age, and year of diagnosis were used to analyze AEs among those with BrMs from primary lung tumors. Year of diagnosis was grouped into prior/post-2013, to account for shifts in treatment paradigms. The results showed nuanced sex-specific AEs. Females diagnosed post-2013 with small-cell, squamous-cell, or other non-small-cell carcinoma BrMs had a higher headache likelihood than males. Males with adenocarcinoma post-2013 were more likely to experience brain herniation. Females aged 76 and older with small-cell BrM exhibited increased vision difficulty risk compared to males of the same age, with no significant difference in other age groups. Males treated for adenocarcinoma faced heightened hemorrhagic stroke risk. This study reveals sex-specific disparities in AEs among older individuals with lung cancer BrMs, varying by histological subtype, age, diagnosis year, and treatment.

Whole-Genome Omics Elucidates the Role of CCM1 and Progesterone in Cerebral Cavernous Malformations within CmPn Networks.

Cerebral cavernous malformations (CCMs) are abnormal expansions of brain capillaries that increase the risk of hemorrhagic strokes, with CCM1 mutations responsible for about 50% of familial cases. The disorder can cause irreversible brain damage by compromising the blood-brain barrier (BBB), leading to fatal brain hemorrhages. Studies show that progesterone and its derivatives significantly impact BBB integrity. The three CCM proteins (CCM1, CCM2, and CCM3) form the CCM signaling complex (CSC), linking classic and non-classic progesterone signaling within the CmPn network, which is crucial for maintaining BBB integrity. This study aimed to explore the relationship between CCM1 and key pathways of the CmPn signaling network using three mouse embryonic fibroblast lines (MEFs) with distinct CCM1 expressions. Omics and systems biology analysis investigated CCM1-mediated signaling within the CmPn network. Our findings reveal that CCM1 is essential for regulating cellular processes within progesterone-mediated CmPn/CmP signaling, playing a crucial role in maintaining microvessel integrity. This regulation occurs partly through gene transcription control. The critical role of CCM1 in these processes suggests it could be a promising therapeutic target for CCMs.

Cardiac Findings Following Cerebrovascular Disease.

Accumulating evidence suggests that cardiac findings after stroke are an important, yet understudied, manifestation of brain-heart interactions. Our aim was to investigate and compare cardiac findings after different cerebrovascular events (acute ischemic stroke, transient ischemic attack, and hemorrhagic stroke). There were 7113 patients screened who were treated between December 2013 and December 2020 at the University Hospital Zurich for ischemic stroke, transient ischemic attack, and hemorrhagic stroke. Seven hundred twenty-one patients without evidence of previous cardiac disease or presumed cardioembolic origin of their cerebrovascular disease and with at least 1 cardiac checkup were included. Clinical reports from the year following disease onset were screened for new cardiac findings, which were categorized as arrhythmia/electrocardiographic changes, myocardial alterations, valvular abnormalities, and coronary perfusion insufficiency. Differences in proportions of findings among groups were analyzed using the Pearson χ2 test or Fisher exact test. ECG changes were observed in 81.7% (n=474) of patients with ischemic stroke, 71.4% (n=70) of patients with transient ischemic attack, and 55.8% (n=24) of patients with hemorrhagic stroke (P<0.001). Myocardial alterations occurred often in all 3 groups (60.9% ischemic stroke [n=353], 59.2% transient ischemic attack [n=58], 44.2% hemorrhagic stroke [n=19]; P=0.396). Cardiac findings are frequent in patients with cerebrovascular disease, even without prior cardiac problems or suspected cardiac cause. Similarities, especially between patients with ischemic stroke and transient ischemic attack, were observed. Our data suggest that all patients with acute cerebrovascular events should receive thorough workup searching for cardiac manifestations.

Disentangling the Inverse LDL-C-hemorrhagic Stroke Association in Chinese Adults with Hypertension: Findings from the Chinese Multi-Provincial Cohort Study.

Why lower low-density lipoprotein cholesterol (LDL-C) was associated with a decreased atherosclerotic cardiovascular disease (ASCVD) risk but an increased hemorrhagic stroke (HS) risk in hypertensive adults remains unclear. We examined whether the inverse LDL-C-HS association partly arises from its effect on ASCVD. We estimated separable effects of LDL-C on HS outside (i.e., separable direct effect) or only through its effect on ASCVD (i.e., separable indirect effect) in hypertensive adults from the Chinese Multi-provincial Cohort Study. We quantified such effects using numbers needed to treat (NNT) to prevent or cause an extra HS based on the restricted mean event-free time till a 25-year follow-up. LDL-C $<$ 70 mg/dL was not associated with an increased HS risk compared to LDL-C $\ge$ 70 mg/dL regarding total and separable direct effects. However, a small separable indirect effect (i.e., NNT to harm: 9722 participants) was noted and validated via a series of sensitivity analyses. Moreover, modified effects were observed, particularly in the 35-49-year age group, men, and those with SBP $\ge$ 140 mm Hg. These results suggest the inverse LDL-C-HS association in hypertensive adults is partly due to its effect on ASCVD. A better understanding of such associations would provide more enlightening into stroke prevention.

Incidence and Predictors of Stroke in Australian Adults With Congenital Heart Disease (2000-2017).

Adults with congenital heart disease (CHD) are at increased risk of stroke but high-quality population level data on stroke incidence in these patients are scant. A retrospective whole-population Western Australian cohort of adultpatients with CHD aged 18 to 64 years was created and followed from January 2000 to December 2017 using linked hospital data. Stroke incidence rates within the adult cohort with CHD were calculated and compared with the general population via direct standardization. A nested case-control design assessed predictors of ischemic and hemorrhagic stroke within the cohort. Among 7916 adults with CHD, 249 (3.1%) incident strokes occurred at a median age of 47 years; 186 (2.3%) ischemic, 33 (0.4%) hemorrhagic and 30 (0.4%) unspecified strokes. Ischemic and hemorrhagic stroke incidence was, respectively, 9 and 3 times higher in adults with CHD than the general population. Absolute risk was low with annual rates of 0.26% (ischemic) and 0.05% (hemorrhagic). Highest rates were observed in adults with shunt and left-sided lesions. Predictors of ischemic stroke in adults with CHD included recent cardiac surgery, left-sided valve repair/replacements, shunt lesions, and traditional risk factors (hypertension, infective endocarditis, peripheral vascular disease, and tobacco use). Mental health disorders and increasing Charlson's comorbidity scores were strongly associated with higher risk of ischemic and hemorrhagic stroke. The CHA2DS2VASc score was associated with ischemic stroke incidence. This study provides the first population-based stroke incidence estimates for adults with CHD in Australia, showing elevated stroke risk across different CHD lesions. It highlights the potential clinical importance of managing comorbidities, especially mental health.

Clinical diagnosis of stroke patients using SIRIRAJ stroke score and Computed Tomography

Background &amp; Objectives: Stroke is a significant cause of disability and death globally, with ischemic and hemorrhagic types. Rapid diagnosis is critical, particularly in resource-limited settings where access to neuroimaging is restricted. Thus, this study aimed to diagnose stroke patients usingthe Siriraj Stroke Score (SSS) and computed tomography at Janaki Medical College TeachingHospital.Materials and Methods: A total of 97 stroke patients presented within 72 hours of onset atJanaki Medical College Teaching Hospital, Nepal, were included in this study. Patients wereclinically assessed using the SSS and subsequently underwent CT brain scanning to confirm thestroke subtype. The SSS was calculated based on consciousness level, headache, vomiting,atheroma markers, and diastolic blood pressure. The results from SSS were compared with the CTscan findings to determine the clinical diagnosis.Results: The study found that 56.7% of the patients had hemorrhagic strokes, with intraparenchymal hematoma being the most common subtype. The SSS showed a strong correlation with CT scan results, particularly for hemorrhagic strokes, where most patients with a score above 1 were accurately diagnosed.Conclusion: The Siriraj Stroke Score is a valuable tool for initial stroke assessment, especially insettings where advanced neuroimaging is not immediately available. The study supports usingSSS in early stroke management, which could improve patient outcomes in resource-limited environments.

Study of serum gamma glutamyl transferase in acute stroke - a single centre experience

Background: Gamma-glutamyl transferase (GGT) is an enzyme involved in oxidative stress and inflammation, which are key mechanisms in the pathogenesis of stroke. Recent evidence suggests serum GGT levels may be associated with the risk and prognosis of acute ischemic stroke. This study aimed to investigate serum GGT levels in patients with acute stroke at a single center in India. Methods: This case-control study included 100 patients (50 with acute stroke and 50 age and sex-matched controls). Patients aged 40 to 80 years and diagnosed with acute stroke (encompassing first-time occurrences of intracerebral hemorrhage, ischemic stroke, and subarachnoid hemorrhage) were included in the study. Serum GGT levels were compared between stroke patients and controls. The association of GGT with various risk factors was also analyzed among cases. Results: The mean age of cases is 60.2±10.07 years. Hemorrhagic stroke was most common and found in 52% of cases. Mean serum GGT levels were significantly higher in stroke patients (55.2540±40.8909 U/l). Higher serum GGT levels were associated with male gender, presence of diabetes, hypertension, dyslipidemia and smoking and were found to be statistically significant (p&lt;0.005). Age and stroke type were found to be not significantly associated with GGT levels. Conclusions: In conclusion, our study findings indicate that elevated serum GGT levels are associated with an increased risk of stroke, particularly in male patients and those with hypertension, dyslipidemia, and diabetes. Further prospective studies are needed to establish the predictive value of GGT for stroke.

Resistant hypertension and the risk of major adverse cardiac and cerebrovascular events in outpatients

Objective: To investigate the prevalence and associated risk of cardiovascular event of resistant hypertension in treated outpatients. Methods: This study was a nationwide multi-center prospective cohort study. The participants were treated outpatients enrolled in the China Nationwide Ambulatory and Home Blood Pressure Registry study of 42 hospitals in 19 provinces across the country from August 2009 to October 2017. Apparent resistant hypertension was defined as uncontrolled office blood pressure (≥140/90 mmHg, 1 mmHg=0.133 kPa) in spite of the use of three antihypertensive drugs or controlled office blood pressure (<140/90 mmHg) with four antihypertensive drugs or more. Subjects diagnosed with uncontrolled office blood pressure were further subdivided as pseudo-resistant hypertension and true resistant hypertension based on 24 h ambulatory blood pressure monitoring. The primary endpoint was fatal and non-fatal cardiovascular and cerebrovascular events, which was a composite endpoint consisting of cardiovascular and cerebrovascular death, ischemic and hemorrhagic stroke, myocardial infarction, coronary artery revascularization, unstable angina, heart failure, and coronary artery stenosis≥50% confirmed by coronary angiography. Secondary outcomes included fatal and non-fatal stroke or cardiac events. Patients with controlled office blood pressure after taking only 1 or 2 antihypertensive drugs were included as control. Kaplan-Meier survival curves, log-rank test, and Cox proportional risk model were used to evaluate the risk of apparent refractory hypertension in relation to cardiovascular and cerebrovascular prognosis. Results: A total of 2 782 treated hypertensive patients, aged (58.1±12.3) years were enrolled, including 1 403 (50.4%) men. The prevalence of apparent and true resistant hypertension was 15.1% (420/2 782) and 10.5% (293/2 782), respectively. Among patients with apparent resistant hypertension, during a median of 5 years follow-up, the cumulative incidence rate was 28.2, 11.2 and 19.1 per 1 000 person-years for fatal and non-fatal cardiovascular events (n=58), stroke (n=24) and cardiac events (n=40), respectively. The Kaplan-Meier curve and log-rank test showed that those patients with true resistant hypertension, had the highest cumulative incidence rate of fatal and non-fatal cardiovascular events, stroke, and cardiac events. Multivariable Cox regression analyses showed that true resistant hypertension was associated with a significantly higher risk of fatal and non-fatal cardiovascular events (HR=1.73, 95%CI 1.17-2.56, P=0.006) and stroke (HR=2.81, 95%CI 1.53-5.17, P=0.001). Conclusion: Resistant hypertension, especially true resistant hypertension, is associated with a higher risk of fatal and non-fatal cardiac and cerebrovascular events.

Navigating the Nexus: Acute Kidney Injury in Acute Stroke - A Prospective Cohort Study.

Acute kidney injury (AKI) is prevalent in patients with acute stroke. Although AKI is linked to poor clinical outcomes, data about its incidence and effect on stroke outcomes is limited. This was a prospective observational study carried out at a single tertiary care center that analyzed the data of 204 consecutive subjects with acute ischemic stroke and intracerebral hemorrhage. Considering serum creatinine at admission as the baseline, AKI was defined as a rise in serum creatinine value of 0.3 mg/dl over 48 h or a percentage increase of at least 50% from baseline over 7 days during hospitalization. The primary outcome was to measure the prevalence of AKI in patients with acute stroke. Secondary outcome measures were all-cause mortality, duration of hospital stay, need for dialysis, and comparison of outcomes in ischemic and hemorrhagic stroke. For both the stroke subtypes, we employed a multivariate logistic regression model, with AKI and hospital mortality being the outcomes. Covariates included gender, age, ventilatory requirement, duration of hospital stay, and National Institutes of Health Stroke Scale score at admission. There were 144 cases of ischemic stroke with 12 deaths (8.3%) and 60 cases of intracranial hemorrhage (ICH) with 22 deaths (36.7%). The mean age was 55 years, 72.6% were males, and AKI complicated 34% of ischemic stroke and 66.7% of ICH hospitalizations. AKI was linked to increased hospital mortality from ischemic stroke (odds ratio [OR] 27.21, 95% CI 3.39-218.13) and hemorrhagic stroke (OR 5.12, 95% CI 1.29-20.28) in multivariate analysis stratified by stroke type. AKI complicates stroke frequently and increases hospital mortality. Additional studies are required to assess if the association is causal and if remedies to prevent AKI would decrease mortality.

JNK2-MMP-9 axis facilitates the progression of intracranial aneurysms

Intracranial aneurysm (IA) can cause subarachnoid hemorrhage or some other hemorrhagic stroke after rupture. Because of the poor outcome in spite of the intensive medical care after the onset of hemorrhage, the development of a novel therapeutic strategy like medical therapy to prevent the progression of the disease becomes a social need. As the reduction of arterial stiffness due to the degeneration of the extracellular matrix via Matrix Metalloproteinases (MMPs) becomes one of the central machineries leading to the progression of IAs through a series of studies, factors regulating the expression or the activity of MMPs could be a therapeutic target. In the present study, specimens from human IA lesions and the animal model of IAs were used to examine the expression of c-Jun N-terminal kinase (JNK) which might exacerbate expressions of MMPs in the lesions to weaken arterial walls resulting in the progression of the disease. In some human IA lesions examined, the expression of p-JNK, the activated form of JNK, could be detected mostly in the medial smooth muscle cells. In IA lesions induced in rats, the activation of JNK was induced during the progression of the disease and accompanied with the activation of downstream transcriptional factor c-Jun and importantly with the expression of MMP-2 or -9. The genetic deletion of Jnk2, not Jnk1, in mice significantly prevented the incidence of IAs with the suppression of the expression of MMP-2 or MMP-9. These results combined together have suggested the crucial role of JNK in the progression of IAs through regulating the expression of MMPs. The results from the present study provides the novel insights about the pathogenesis of IA progression and also about the therapeutic target.

GGC repeat expansions in NOTCH2NLC cause uN2CpolyG cerebral amyloid angiopathy.

The expansion of GGC repeats within NOTCH2NLC leads to the translation of the uN2CpolyG protein, the primary pathogenic factor in neuronal intranuclear inclusion disease (NIID). This study aims to explore the deposition of uN2CpolyG as an amyloid in the vessel wall, leading to uN2CpolyG cerebral amyloid angiopathy (CAA)-related cerebral microbleeds (CMBs). A total of 97 patients with genetically confirmed NIID were enrolled in this study. We analyzed the presence of CMBs using susceptibility-weighted imaging sequences and compared general clinical information, cerebrovascular risk factors, stroke history, antiplatelet medication use, and MRI features between NIID patients with and without CMBs. We further performed hematoxylin and eosin (H&E), Perl's, Congo red, and Thioflavin S staining, ubiquitin, p62 and uN2CpolyG immunostaining on brain tissue obtained from four NIID patients. A total of 354 CMBs were detected among 41 patients with NIID, with nearly half located in the deep brain, one-third in the lobes, and approximately 20% in the infratentorial area. No significant differences in cerebrovascular disease risk factors or history of antiplatelet drug use were observed between patients with and without CMBs. However, patients with CMBs suffered a higher incidence of previous ischemic and hemorrhagic stroke events. This group also had a higher incidence of recent subcortical infarcts and a higher proportion of white matter lesions in the external capsule and temporal pole. Conversely, patients without CMBs showed higher detection of high signals at the corticomedullary junction on diffusion-weighted imaging and more pronounced brain atrophy. H&E staining showed blood vessel leakage and hemosiderin-laden macrophage clusters, and Prussian blue staining revealed brain tissue iron deposition. CMBs occurred more frequently in small vessels lacking intranuclear inclusions, and extensive degeneration of endothelial cells and smooth muscle fibres was observed mainly in vessels lacking inclusions. Congo red-positive amyloid deposition was observed in the cerebral vessels of NIID patients, with disordered filamentous fibres appearing under an electron microscope. Additionally, the co-localization of Thioflavin S-labeled amyloid and uN2CpolyG protein in the cerebral vascular walls of NIID patients further suggested that uN2CpolyG is the main pathogenic protein in this form of amyloid angiopathy. In conclusion, we reviewed patients with GGC repeat expansion of NOTCH2NLC from a novel perspective, providing initial clinical, neuroimaging, and pathological evidence suggesting that uN2CpolyG may contribute to a distinct type of CAA.

Efficacy and safety of aspirin plus clopidogrel versus aspirin alone in ischemic stroke or high-risk transient ischemic attack: A meta-analysis of randomized controlled trials.

Background: Antiplatelet therapy plays an important role in reducing the risk of stroke recurrence in patients with mild ischemic stroke or high-risk transient ischemic attack (TIA). However, data regarding the effectiveness and safety of using aspirin plus clopidogrel in dual antiplatelet therapy (DAPT) compared to aspirin alone in mild ischemic stroke is limited. Methods: PubMed/MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared DAPT to aspirin alone started within 72 hours in mild ischemic stroke or high-risk TIA. We used a random effects model to pool risk ratios (RRs) along with 95% CIs for clinical outcomes. Results: Four RCTs with 16,547 patients were included in this study. DAPT significantly reduced the risk of recurrent stroke by 26% (RR: 0.74; 95% CI: 0.67-0.83; p < 0.00001), ischemic stroke by 28% (RR: 0.72; 95% CI: 0.65-0.80; p < 0.00001), and major adverse cardiovascular events (MACE) by 24% (RR: 0.76; 95% CI: 0.68-0.84; p < 0.00001) compared to aspirin monotherapy. However, DAPT was associated with a significantly increased risk of moderate or severe bleeding (RR: 1.88; 95% CI: 1.10-3.23; p = 0.02) compared to aspirin alone. No significant differences were observed for hemorrhagic stroke (RR: 1.77; 95% CI: 0.96-3.29; p = 0.07), all-cause mortality (RR: 1.25; 95% CI: 0.87-1.80; p = 0.23), cardiovascular mortality (RR: 1.38; 95% CI: 0.81-2.33; p = 0.23), and myocardial infarction (RR: 1.63; 95% CI: 0.77-3.46; p = 0.20). Conclusion: DAPT involving aspirin plus clopidogrel reduces stroke recurrence and MACE but can lead to an increased risk of moderate or severe bleeding compared to aspirin monotherapy. (PROSPERO ID: CRD42024499310).

Electrolytes Status in Acute Stroke Patient in Rajshahi Medical College Hospital

Background: Stroke is a major cause of mortality and morbidity worldwide, significantly impacting patients and healthcare systems. Electrolyte imbalances are common in acute stroke patients and can influence clinical outcomes. This study investigates the electrolyte status in acute stroke patients admitted to Rajshahi Medical College Hospital Objective: To evaluate the electrolyte status (sodium and potassium levels) in acute stroke patients and its association with stroke types (Ischaemic and haemorrhagic) and clinical outcomes. Method: A cross-sectional study was conducted over two years (July 2017 to June 2019) in the Medicine and Neuromedicine Department of Rajshahi Medical College Hospital. A total of 104 acute stroke patients were included. Serum sodium and potassium levels were measured upon admission. Sociodemographic data, stroke types, and electrolyte levels were analyzed. Results: Among the 104 stroke patients, 71 (68.27%) had ischaemic stroke, and 33 (31.73%) had haemorrhagic stroke. The age distribution was highest in the 50-60 years group (34.62%). Males comprised 58.65% of the patients. Sodium levels were normal in 61.54% of patients, high in 2.88%, and low in 35.58%. Potassium levels were normal in 68.27% of patients, high in 10.58%, and low in 21.15%. No significant difference was found in sodium (p&gt;0.05) and potassium (p&gt;0.05) levels between ischaemic and haemorrhagic stroke patients. Conclusions: Electrolyte imbalances are prevalent in acute stroke patients, but no significant differences were observed between ischaemic and haemorrhagic stroke types. Regular monitoring and correction of electrolytes are crucial in managing stroke patients to improve outcomes.

C-reactive protein (CRP) and lactate dehydrogenase (LDH) as functional outcome predictors in stroke patients

Stroke is a neurologic disorder with high mortality and disability. Its pathophysiology is associated with vascular inflammation. However, studies between vascular inflammatory markers and stroke outcomes are still limited. This study aimed to investigate the association between inflammatory markers and functional outcomes of stroke. This was a retrospective cohort study involving all stroke patients at the Dr. Sardjito General Hospital, Yogyakarta from October 2020 to August 2021 who meet the inclusion and exclusion criteria. Mann-Whitney was used for bivariate analysis, followed by multivariate analysis. A total of 269 subjects, with 213 infarcts (79.2%) and 56 hemorrhagic (20.8%) strokes. There were 83 subjects deceased (30.9%), with 66 infarct (31%) and 17 hemorrhagic (30.4%) strokes. High CRP levels had significant and independent associations with worse GCS, ADL, IADL, NIHSS, BI, SSGM, MRS, and higher mortality rates (p &lt; 0.05). High LDH levels had a significant and independent association with worse GCS scores and higher mortality rates (p &lt; 0.05). Sub-analysis showed high CRP and LDH had associations with high mortality rates in infarct (p &lt; 0.001), but only CRP (p = 0.029) had associations with high mortality rates in hemorrhagic. There was no significant association between fibrinogen and procalcitonin with stroke outcomes (p &gt; 0.05). Cox-regression analysis showed CRP&gt;24.5 mg/dL and LDH &gt;300U/L associated with hazard ratios of 3.2 (p &lt; 0.001) and 1.65 (p = 0.026). In conclusion. high CRP and LDH levels are associated with mortality rates in stroke patients.

Hypertension Prevalence, Treatment, and Control 90 Days After Acute Stroke Among Mexican American and Non-Hispanic White Adults.

High blood pressure (BP) increases recurrent stroke risk. We assessed hypertension prevalence, treatment, control, medication adherence, and predictors of uncontrolled BP 90 days after ischemic or hemorrhagic stroke among 561 Mexican American and non-Hispanic White (NHW) survivors of stroke from the BASIC (Brain Attack Surveillance in Corpus Christi) cohort from 2011 to 2014. Uncontrolled BP was defined as average BP ≥140/90 mm Hg at 90 days poststroke. Hypertension was uncontrolled BP or antihypertensive medication prescribed or hypertension history. Treatment was antihypertensive use. Adherence was missing zero antihypertensive doses per week. We investigated predictors of uncontrolled BP using logistic regression adjusting for patient factors. Median (interquartile range) age was 68 (59-78) years, 64% were Mexican American, and 90% of strokes were ischemic. Overall, 94.3% of survivors of stroke had hypertension (95.6% Mexican American versus 92.0% non-Hispanic White; P=0.09). Of these, 87.9% were treated (87.3% Mexican American versus 89.1% non-Hispanic White; P=0.54). Among the total population, 38.3% (95% CI, 34.4%-42.4%) had uncontrolled BP. Among those with uncontrolled BP prescribed an antihypertensive, 84.5% reported treatment adherence (95% CI, 78.8%-89.3%). Uncontrolled BP 90 days poststroke was less likely in patients with stroke who had a primary care physician (adjusted odds ratio [aOR], 0.45 [95% CI, 0.24-0.83]; P=0.01), greater stroke severity (aOR per-1-point-higher National Institutes of Health Stroke Scale score, 0.96 [95% CI, 0.93-0.99]; P=0.02), or more depressive symptoms (aOR per-1-point-higher Personal Health Questionnaire Depression Scale-8 score, 0.95 [95% CI, 0.92-0.99] among those with a history of hypertension at baseline; P=0.009). Greater than one third of survivors of stroke have uncontrolled BP at 90 days poststroke in this population-based study. Interventions are needed to improve BP control after stroke.