Deterioration In Ischemic Stroke Research Articles

Cognitive-Enhancing Effect of Marine Brown Algae-Derived Phenolics through S100B Inhibition and Antioxidant Activity in the Rat Model of Ischemic Stroke.

Cognitive impairments are frequently reported after ischemic strokes. Novel and effective treatments are required. This study aimed to develop a functional ingredient obtained from marine algae and to determine the effect of the extract on antioxidative stress, as well as neuroprotective effects, in a rat model of MCAO-induced ischemic stroke. Among the selected marine algal extracts, Sargassum polycystum displayed the highest total phenolic content and antioxidative potential, and was subsequently used to evaluate cognitive function in rat models of ischemic stroke. The S. polycystum extract, administered at doses of 100, 300, and 500 mg/kg BW, significantly improved cognitive function by enhancing cognitive performance in the Morris water maze and novel object recognition tests. Biochemical changes revealed that providing S. polycystum increased the activities of SOD, CAT, and GSH-Px by 52.48%, 50.77%, and 66.20%, respectively, and decreased the concentrations of MDA by 51.58% and S100B by 36.64% compared to the vehicle group. These findings suggest that S. polycystum extract may mitigate cognitive impairment in ischemic stroke by reducing oxidative stress and inhibiting S100B expression, thus highlighting its potential as a functional ingredient for drugs and nutraceuticals aimed at neuroprotection.

Safety and Effectiveness Analysis of Endovascular Treatment versus Standard Medication Treatment in Patients with Progressive Acute Ischemic Stroke with Large Vessel Occlusion Stroke in the Ultra-Late Time Window: A Propensity Score Matched Cohort Study

The time from onset to symptom deterioration in ischemic stroke often exceeds 24hours, and this ultra-late time window is excluded from the endovascular treatment (EVT) guideline. This study aimed to explore the safety and efficacy of EVT in progressive acute ischemic stroke with large vessel occlusion stroke patients with onset to symptom deterioration times of 24 hours-7days. Progressive stroke patients with time window of 24 hours-7days treated at our hospital over the past 6years were retrospectively collected. Patients were categorized into EVT and standard medication treatment (SMT) groups based on the treatment approach. Patients were matched using propensity score matching. Safety outcomes primarily included 3-month mortality and symptomatic intracranial hemorrhage; efficacy outcome primarily included functional independence (3-month modified Rankin scale≤2). A total of 396 patients were included in the study, with 86 (21.7%) in EVT and 310 (78.3%) in SMT group. There were 140 remaining after propensity score matching, with 70 in each group (50%). Compared to SMT group, EVT group had higher functional independence (52.9% vs. 15.7%, odds ratio [OR]=7.504, 95% confidence interval [CI] 2.141-14.093, P < 0.001) and lower 3-month mortality (14.3% vs. 40.0%, OR=0.412, 95% CI 0.099-0.856, P < 0.001). EVT was also associated with higher symptomatic intracranial hemorrhage (25.7% vs. 5.7%, OR=9.926, 95% CI 1.874-36.547, P < 0.001). For patients with progressive acute ischemic stroke with large vessel occlusion in the ultra-late time window, EVT remains a viable treatment approach.

Study of Biochemical Predictors of Early Neurological Deterioration in Ischemic Stroke in a Tertiary Care Hospital.

Background and objective Early neurological deterioration (END) following acute ischemic stroke (AIS) poses a significant clinical challenge, often leading to increased disability and mortality. This study aimed to investigate the association between specific biomarkers (lactate dehydrogenase (LDH), ferritin,erythrocyte sedimentation rate (ESR),C-reactive protein (CRP), homocysteine) and the occurrence of END in ischemic stroke patients in a tertiary care hospital. Materials and methods Across-sectional hospital-basedstudy was conducted at Dr. D. Y. Patil Medical College and Hospital, Pune, from July 2022 to April 2024. Patients aged 18 and above with confirmed ischemic stroke were included, while those with hemorrhagic stroke, intracranial tumors, mass effect with midline shift, or extensive cerebral edema were excluded. Upon admission, patients were assessed using the National Institutes of Health Stroke Scale (NIHSS) and monitored daily for seven days. Biomarkers, including LDH, ferritin, ESR, CRP, and homocysteine, were measured, and patients were categorized into those with END and without END. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, New York). Results Out of 100 patients, 12% experienced END. The mean age of patients with END was 53.50 ± 11.20 years, compared to 53.62 ± 11.74 years in those without END (p = 0.790). Males constituted 91.7% of the END group and 73.9% of the non-END group (p = 0.284). A significant association was found between END and alcohol use (41.7% in END vs. 12.5% in non-END, p = 0.010) and tobacco use (41.7% in END vs. 11.4% in non-END, p = 0.010). The mean NIHSS scores were significantly higher in the END group on day 1 (11.58 ± 3.06 vs. 7.69 ± 3.98,p = 0.002) and on day 3 (13.92 ± 3.15 vs. 6.00 ± 3.65, p = 0.001). Biomarker analysis showed a significant difference in the mean vitamin B12 levels between END and non-END groups (93.17 ± 48.58 vs. 183.45 ± 349.33, p = 0.025). Conclusion Our study identified significant predictors of ENDin ischemic stroke patients, including alcohol and tobacco use, higher initial NIHSS scores, and elevated levels of LDH, ferritin, ESR, CRP, and homocysteine, along with low vitamin B12 levels. These findings highlight the importance of routine biochemical assessments and personalized treatment plans in managing AIS, emphasizing lifestyle changes and nutritional support to improve outcomes. Limitations include the single-center design, small sample size, and lack of long-term follow-up data. Future research should validate these findings in larger, multicenter studies and explore their long-term impact on stroke recovery.

Association of plasma metals with resting-state functional connectivity in ischemic stroke

BackgroundMetal exposure has long been considered a significant risk factor for ischemic stroke. However, existing data on the effects of metal exposure on brain function in ischemic stroke are limited. Therefore, this study aimed to explore the correlation between exposure to various metals and changes in resting-state functional connectivity (rs-FC) in ischemic stroke patients. MethodsThis study included 28 acute ischemic stroke patients with hemiplegia and 28 matched healthy controls (HCs). All participants underwent T1-weighted MRI and 3.0 T resting-state functional magnetic resonance imaging (fMRI). After MRI acquisition, the rs-FC between 137 cortical and subcortical regions was extracted and preprocessed. Plasma levels of 19 metals were measured using inductively coupled plasma mass spectrometry (ICP-MS). The Bayesian kernel machine regression (BKMR) model and the weighted quantile sum regression (WQS) model were used to assess the overall effect of metal mixture exposure. The severity of neurological deficits in each acute ischemic stroke patient was evaluated using the National Institutes of Health Stroke Scale (NIHSS). Additionally, the associations between exposure to various metals and modifications in brain functional connectivity were determined using Pearson or Spearman correlation analysis. ResultsBilateral brain connectivity was significantly decreased compared to controls and was associated with neurological impairment in ischemic stroke. In patients with ischemic stroke, the plasma concentrations of Cr (p < 0.001), Cu (p = 0.004), As (p = 0.010), Cs (p = 0.046), Rb (p = 0.041), and Sb (p = 0.001) were significantly higher than those in the HCs, whereas the plasma Tl concentrations (p = 0.022) were significantly lower. The results of the BKMR and WQS models showed that combined exposure to metal mixtures was linked to a higher risk of ischemic stroke. Cr was positively correlated with the rs-FC between the left Rolandic_Oper and the left Supp_Motor_Area (r = 0.414, p = 0.029), while negatively correlated with the rs-FC between the right Parietal_Inf and the left supramarginal (r = −0.398, p = 0.037). Cu was negatively correlated with the rs-FC between the left paracentral lobule and the left thalamus (r = −0.409, p = 0.031). Tl was positively correlated with the rs-FC between the right Parietal_Inf and the left supramarginal cortex (r = 0.590, p = 0.001). A negative correlation was observed between Cs and rs-FC between the right Cingulate_Mid and left Occipital_Sup (r = −0.429, p = 0.024). Sb was negatively correlated with the rs-FC between the left Parietal_Inf and the right SupraMarginal (r = −0.384, p = 0.044), the right Parietal_Inf and the left SupraMarginal (r = −0.583, p = 0.001), and the left SupraMarginal and the right SupraMarginal (r = −0.377, p = 0.048). ConclusionPlasma levels of Cr, Cu, Tl, Cs, and Sb were associated with altered rs-FC in brain regions related to motor control, sensory integration, executive function, language processing, and emotional regulation in ischemic stroke patients with basal ganglia infarction.

Abstract 21: Similarity in the Changes of Brain Myeloid Transcriptome Signature is Shared Between Ischemic Stroke and Chronic Inflammation Caused by Diabetes Mellitus

Introduction: Ischemic stroke (IS) is a pressing global health concern. Diabetes mellitus not only heightens the risk of IS but also aggravates its outcomes. There is established evidence that neutrophil infiltration is involved in inflammation after stroke through various mechanisms, such as activating neutrophil extracellular traps. We aimed to examine the factors that contribute to the deterioration of IS in diabetic mice focusing on mechanisms underlying immune cell infiltration by single cell RNA sequencing (scRNAseq) of brain before and after stroke. Methods: Experimental stroke was induced using the distal middle cerebral artery occlusion (dMCAO) model. db/db mice were used to model type 2 diabetes and obesity, while db/+ mice served as euglycemic controls. Mononuclear cells from ipsilateral mouse brains were isolated 3 days post-dMCAO or sham surgery with the Percoll gradient following enzymatic digestion. Transcriptomic analysis was performed using scRNAseq from db/+ sham, db/db sham, db/+ stroke, and db/db stroke. Fluorescence-activated cell sorting (FACS) and immunofluorescence (IF) staining were conducted to validate the changes detected in the transcriptome results. Results: Prior to the onset of stroke, db/db mice exhibited changes in gene expression in endothelial cells and myeloid cells including macrophages, monocytes, and microglia, mirroring patterns of changes after stroke. Among the macrophage subpopulation in particular, db/db sham and db/+ stroke mice shared an overlap of 638/901 (70.8%) differentially expressed genes compared to db/+ sham. Gene enrichment analysis indicated predominant upregulation of genes linked to leukocyte migration and neutrophil chemotaxis. FACS revealed a heightened neutrophil presence in the brain parenchyma of diabetic mice before stroke, and further elevated after stroke compared to control mice. Specifically, the increased expression of anaphylatoxin receptor C3aR and complement C3 shown by IF corroborated with the transcriptomic signature, supporting a role of complement activation and myeloid cell transmigration. Conclusions: Our findings provide valuable insights into the mechanisms whereby diabetes potentially escalates neutrophil infiltration post-stroke.

Correlation between Atherogenic Index of Plasma and Lipid Profile with Cognitive Function and Their Effect on Outcome in Ischemic Stroke Patients

Dyslipidemia is one of the main risk factors for both ischemic stroke and cognitive impairment. Atherogenic index of plasma (AIP) has been shown to correlate with mortality and clinical outcomes in stroke, but studies about its association with cognitive impairment in ischemic stroke is still limited. We aimed to determine the correlation between AIP and lipid profile and cognitive function and their effect on outcome in ischemic stroke patients. A cross-sectional study involving 50 ischemic stroke patients in the Haji Adam Malik General Hospital was conducted from August 2021 to March 2022. We measured the cholesterol level and calculated the AIP then divided them into 3 risk categories which were high (AIP&gt;0.21); intermediate (AIP&gt;0.11and ≤0.21) and low (≤0.11). We performed cognitive assessment and stroke outcome at the 7th day of stroke onset. Data analysis was conducted with Spearman correlation test. The subjects were predominantly male (60%) with median age of 55 (34-68) years. Most of the subjects had AIP level of high risk (54%) and were cognitively impaired (66%). There was no significant association between AIP and both global cognition and each cognitive domain. However, there were significant negative correlations between total cholesterol (r=-0.31, p=0.03) and LDL-C level (r=-0.30, p=0.03) and attention. There was also a significant negative correlation between cognitive function and stroke outcome (r=-0.61, p=0.01). Higher total cholesterol and LDL-C levels showed negative correlation with cognitive function, mainly attention. Poorer cognitive function correlated with worse outcome in ischemic stroke patients.

D-dimer to fibrinogen ratio predicts early neurological deterioration in ischemic stroke with atrial fibrillation

IntroductionThe D-dimer to fibrinogen ratio (DFR) is a good indicator of clot-producing activity in thrombotic disease, but its clinical usefulness in stroke patients with nonvalvular atrial fibrillation (NVAF) has not been studied. We evaluated the association between the DFR and early neurological deterioration (END) in acute ischemic stroke (AIS) patients with NVAF. MethodsWe included consecutive AIS patients with NVAF between 2013 and 2015 from the registry of a real-world prospective cohort from 11 large centers in South Korea. END was defined as an increase ≥2 in the total NIHSS score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. The DFR was calculated as follows: DFR = D-dimer (mg/L)/fibrinogen (mg/dL) x 100. ResultsA total of 1018 AIS patients with NVAF were evaluated. In multivariable logistic regression analysis, the highest DFR tertile was closely associated with END (adjusted odds ratio [aOR] = 2.14, 95 % confidence interval [CI]: 1.24–3.69). Hypertension (aOR = 1.71, 95 % CI: 1.09–2.70), initial NIHSS score (aOR = 1.05, 95 % CI: 1.02–1.07) and use of anticoagulants (aOR = 0.41, 95 % CI: 0.28–0.60) were also correlated with END. In addition to END, the DFR was correlated with discharge NIHSS and modified Rankin Scale (mRS) scores and the 3-month mRS score. ConclusionsHigh DFR values were associated with END in AIS patients with NVAF. As the DFR is an indicator directly related to the main pathological mechanism of NVAF patients (fibrinolysis and coagulation), it may be useful in predicting their prognosis.

Baseline platelet count may predict short-term functional outcome of cerebral infarction

Background and aimsPlatelets play an important role in homeostasis however, they have also been associated with increased mortality after myocardial infarction. In the present study, we investigated whether platelet count is associated with differences in the short-term prognosis at the time of hospital discharge and early neurological deterioration in ischemic stroke patients.MethodsPatients with ischemic stroke were enrolled from among 661 cerebrovascular disease patients admitted between January 2018 and December 2020. Patients who received hyperacute treatment, had a pre-onset modified Rankin scale (mRS) ≥ 3, transient ischemic attack, or active malignant disease were excluded. The platelet count was divided into quartiles (Q1-4) according to the number of patients, and the relationship between platelet count and prognosis was assessed using multivariable analysis.ResultsIn total, 385 patients were included in the study. Regarding the functional outcome by platelet count, there was a significant increase in mRS ≥ 3 at discharge in the Q4 (range: 243–1327 × 109/L, p = 0.013, ORs: 1.674, 95%CI: 1.253–6.681) group compared to the Q3 (range: 205–242 × 109/L) group even after adjusting for factors with P < 0.2 in univariate analysis. Furthermore, the frequency of neurological deterioration (NIHSS ≥ 4) within 1 week was significantly lower in the Q3 group than in the Q1 (range; 19–173 × 109/L) and Q4 groups even after adjustment (Q1; p = 0.020 ORs: 6.634, 95%CI: 1.352–32.557, Q4; p = 0.007 ORs: 8.765, 95%CI: 1.827–42.035).ConclusionPlatelet count at onset may affect the prognosis of cerebral infarction and early neurological deterioration. This study may help clarify the pathogenesis of cerebral infarction to improve prognosis.

Knockdown of NRSF Alleviates Ischemic Brain Injury and Microvasculature Defects in Diabetic MCAO Mice.

Diabetes is one of the well-established risk factors of stroke and is associated with a poor outcome in patients with stroke. Previous studies have shown that the expression of neuron restrictive silencer factor (NRSF) is elevated in diabetes as well as ischemic stroke. However, the role of NRSF in regulating an outcome of diabetic ischemic stroke has not been completely understood. Here, we hypothesized that diabetes-induced NRSF elevation can aggravate brain injury and cognition impairment in ischemic stroke. The diabetic ischemic stroke mice model was established by 8 weeks of high-fat-diet feeding and 5 days of streptozotocin injection followed by 30 min of middle cerebral artery occlusion (MCAO). We found that diabetes enhanced the MCAO-induced elevation of NRSF in the hippocampus in accompany with an elevation of its corepressors, HDAC1, and mSin3A, and decrease of β-TrCP. By using histological/immunofluorescence staining and neurobehavioral testing, our results showed that the brain damage and learning/memory impairment were aggravated in diabetic ischemic mice but significantly attenuated after stereotaxic injection of NRSF-shRNA. Meanwhile, by performing whole-brain clearing with PEGASOS, microvascular reconstruction, western blotting, and ELISA, we found that NRSF-shRNA markedly alleviated the vasculature disorders and rescued the suppression of NRP-1, VEGF, and VEGFR2 in the hippocampus of diabetic ischemic mice. Therefore, our results demonstrated for the first time that the elevation of hippocampal NRSF plays an important role in alleviating brain injury and cognitive disabilities in diabetic ischemic mice, potentially via the reduction of NRP-1/VEGF signaling.

DL-3-n-butylphthalide promotes hippocampal neurogenesis and reduces mossy fiber sprouting in chronic temporal lobe epilepsy rats

BackgroundA decrease in hippocampal neurogenesis is considered an important cause of cognitive impairment, while changes in mossy fiber sprouting are closely related to development of spontaneous recurrent seizures in chronic temporal lobe epilepsy (TLE). Racemic l-3-n-butylphthalide (DL-NBP) can alleviate cognitive impairment in ischemic stroke and Alzheimer’s disease by promoting neurogenesis. DL-NBP treatment can also improve cognitive function and reduce seizure incidence in chronic epileptic mice. However, the mechanisms of action of DL-NBP remain unclear. The aim of the present study was to examine the effects of DL-NBP on mossy fiber sprouting, hippocampal neurogenesis, spontaneous epileptic seizures, and cognitive functioning in the chronic phase of TLE.MethodsNissl staining was used to evaluate hippocampal injury, while immunofluorescent staining was used to analyze hippocampal neurogenesis. The duration of spontaneous seizures was measured by electroencephalography. The Morris water maze was used to evaluate cognitive function. Timm staining was used to assess mossy fiber sprouting.ResultsTLE animals showed reduced proliferation of newborn neurons, cognitive dysfunction, and spontaneous seizures. Treatment with DL-NBP after TLE increased the proliferation and survival of newborn neurons in the dentate gyrus, reversed the neural loss in the hippocampus, alleviated cognitive impairments, and decreased mossy fiber sprouting and long-term spontaneous seizure activity.ConclusionsWe provided pathophysiological and morphological evidence that DL-NBP might be a useful therapeutic for the treatment of TLE.

Abstract P798: Antimicrobial Protein Reg3a and Network Inflammatory Proteins Are Predictive of Infarct Volume and Functional Impairment in Ischemic Stroke

Introduction: Regenerating Family Member 3 Alpha (REG3A) is an antimicrobial protein secreted by the intestine and pancreas. REG3A is involved in immune-mediated inflammatory responses and helps maintain homeostasis of the gut microbiome. REG3A is elevated in patients with ischemic stroke, but its role within the gut-brain axis during stroke remains unclear. Our aim was to examine the association of plasma REG3A levels with other signaling proteins in systemic plasma during stroke, and its correlation with clinical outcomes of ischemic stroke. Methods: Intracranial and systemic plasma samples from n=25 thrombectomy subjects underwent Proximity Extension Assay via Olink Proteomics. REG3A levels and inflammatory markers were examined using bivariate regressions. Stepwise regression determined the predictability of infarct volume by REG3A. Two-tailed t-tests were used to examine the relationship between the National Institutes of Health Stroke Scale (NIHSS) and levels of REG3A. Results: Increased expression of systemic REG3A correlated with increases in infarct volume (p=.009, R=.514). Stepwise regression predicting infarct volume yielded a model including REG3A and systemic proteins such as CCL19, IL15, and IL1α (P&lt;.001, R=.980). NIHSS scores corresponding to moderate-severe/severe strokes had increased intracranial REG3A (p&lt;.05) and increased ratios of intracranial:systemic REG3A expression (p=.05). Conclusions: Within a network of proteins, REG3A is predictive of increased infarct volume and decreased function. Studies suggest that IL17 and IL6 induce REG3A expression. Subsequent REG3A can interact with NFkB, which transcriptionally regulates CCL19, IL1α, and IL15. In the intestine, REG3A regulates microbial synthesis of fatty acids and inflammatory processes. Fatty acids suppress cytokines such as IL6 and IL1α and are reportedly neuroprotective in stroke. Increase of systemic REG3A may reflect cellular responses to gut dysbiosis and inflammation triggered from ischemic stroke. Future studies will examine prognostic and therapeutic potential of the REG3A pathway in large vessel occlusive stroke.

Role of long noncoding RNA MEG3/miR-378/GRB2 axis in neuronal autophagy and neurological functional impairment in ischemic stroke

Autophagy has been shown to maintain neural system homeostasis during stroke. However, the molecular mechanisms underlying neuronal autophagy in ischemic stroke remain poorly understood. This study aims to investigate the regulatory mechanisms of the pathway consisting of MEG3 (maternally expressed gene 3), microRNA-378 (miR-378), and GRB2 (growth factor receptor-bound protein 2) in neuronal autophagy and neurological functional impairment in ischemic stroke. A mouse model of the middle cerebral artery occluded-induced ischemic stroke and an in vitro model of oxygen-glucose deprivation-induced neuronal injury were developed. To understand the role of the MEG3/miR-378/GRB2 axis in the neuronal regulation, the expression of proteins associated with autophagy in neurons was measured by Western blotting analysis, and neuron death was evaluated using a lactate dehydrogenase leakage rate test. First, it was found that the GRB2 gene, up-regulated in middle cerebral artery occluded-operated mice and oxygen-glucose deprivation-exposed neurons, was a target gene of miR-378. Next, miR-378 inhibited neuronal loss and neurological functional impairment in mice, as well as neuronal autophagy and neuronal death by silencing of GRB2. Confirmatory in vitro experiments showed that MEG3 could specifically bind to miR-378 and subsequently up-regulate the expression of GRB2, which in turn suppressed the activation of Akt/mTOR pathway. Taken together, these findings suggested that miR-378 might protect against neuronal autophagy and neurological functional impairment and proposed that a MEG3/miR-378/GRB2 regulatory axis contributed to better understanding of the pathophysiology of ischemic stroke.

Abstract WP497: Investigation of Cognitive Impairment in Ischemic Stroke Patients After Endovascular Treatment in Acute Phase and at 6 Months Follow-Up

Purpose and Objective: There have been limited reports that focused on cognitive impairment in acute ischemic stroke after endovascular treatment. The aim of this study, therefore, was to investigate cognitive function in patient after endovascular treatment in acute phase and at 6 months follow-up. Method: In this prospective study, from December 2016 to November 2018, the patients who were diagnosed as ischemic stroke with occlusion of the internal carotid artery and of the middle cerebral artery and treated with endovascular treatment were enrolled. Cognitive function was assessed with the Montreal Cognitive Assessment (MoCA-J) test within 5 days of onset and at 6 months follow-up. We defined cognitive impairment as a score of &lt;24 in MoCA-J. Results: 150 patients were enrolled. MoCA-J was feasible in 69 patients (median 76 years; 49 female) (46%), in acute phase (Figure A). 63 patients (91%) had cognitive impairment and no significant differences were found in the naming and the abstraction domains between MoCA-J &lt;24 group and ≧24 group. At 6 months follow-up, 48 patients (median 72 years; 12 female) were assessed with MoCA-J and 35 patients (73%) had cognitive impairment. However, only one patient scored less at 6 months follow-up than in acute phase (Figure B), which resulted in the significant increase in the median MoCA-J score (7 vs. 21, P&lt;0.05) (Figure C) and in all the domains except for the language (P=0.078) (Figure D). Conclusion: In acute phase of ischemic stroke after endovascular treatment, MoCA-J was feasible in about 45%, in which 91% had cognitive impairment. However, at 6 months follow-up, the median MoCA-J score was significantly higher and less number of patients had cognitive impairment. The present results suggest that cognition recovers with time after endovascular treatment in ischemic stroke.

Epileptic activity in neurological deterioration after ischemic stroke, a continuous EEG study

ObjectiveDespite improvement in acute stroke care, almost 40% of patients with ischemic stroke present neurological deterioration. Neurological deterioration is associated with higher death and dependency rates. Neurological deterioration mechanisms are unknown, and half of neurological deterioration remains unexplained. We postulate that a substantial proportion of neurological deterioration in ischemic stroke is associated with periodic discharges/non-convulsive seizures that negatively impact the recovery of ischemic stroke and worsen symptoms. MethodsRetrospective review of 24 h continuous EEG monitoring (cEEG) performed for neurological deterioration in the stroke unit of a tertiary academic centre. ResultsEighty-one patients were included. cEEG detected epileptic activities in 44% of cases (Non-convulsive seizures/non-convulsive status epilepticus: 10/81 (12%), periodic discharges: 17/81 (21%) and sporadic epileptiform discharges in 14/81 (17%)). The proportion of patients who did not receive recanalization therapy was significantly higher in the NCSE/NCSz/PDs group than in the group devoid of NCSE/NCSz/PDs: 17/22 (77%) vs 13/59 (22%); p < 0,001. Treatment of Non-convulsive seizures /non-convulsive status epilepticus and periodic discharges was followed by EEG improvement in respectively 7/8 and 10/16 of treated patients. ConclusionsNon-convulsive seizures /non-convulsive status epilepticus /periodic discharges are associated to neurological deterioration after ischemic stroke. SignificanceTreatment of Non-convulsive seizures /non-convulsive status epilepticus and periodic discharges, if such patterns are detected, could help prevent adverse metabolic consequences of epileptic activities on ischemic brain tissue.

Молекулярные биомаркеры когнитивных нарушений при ишемическом инсульте

Молекулярные биомаркеры когнитивных нарушений при ишемическом инсульте

Investigating patterns of memory impairment in ischemic stroke in an iranian population

ABSTRACTUp until the date of this research, studies have examined poststroke cognitive impairments in attention, memory, and executive functions. In this study, we investigated the occurrence of memory problems in various patterns of memory in ischemic stroke patients in an attempt to determine specific memory profiles of the patients. The goal was to determine the severity and patterns of memory impairments in ischemic stroke patients and to identify specific profiles of memory impairments in stroke patients, in order to help therapists to develop more appropriate memory rehabilitation programs for the patients. The sample consisted of 35 patients with ischemic stroke. Thirty-five individuals who were matched with the patients were selected as the control group. Demographic questionnaires, subscales of the Wechsler Memory Scale-III (WMS-III), including logical memory I and II and visual reproduction I and II, digit span from the Wechsler Adult Intelligence Scale-R (WAIS-R), and the Corsi span test were administered to both of the patients and control groups. Multivariate analysis of covariance (MANCOVA) was carried out to unveil possible differences in memory between the two groups. The mean scores of different memory patterns were significantly higher in the control group comparing to the patient group (p < 0.05). Among different aspects of memory, visual long-term memory and visual short-term memory had the largest effect sizes. Substantial impairments were also found in visual short-term memory, visuospatial short-term memory, and visual long-term memory. The findings suggest that the stroke patients have identifiable patterns of memory impairment.

Time to Neurological Deterioration in Ischemic Stroke.

Neurological deterioration (ND) is common, with nearly one-half of ND patients deteriorating within the first 24 to 48 hours of stroke. The timing of ND with respect to ND etiology and reversibility has not been investigated. At our center, we define ND as an increase of 2 or more points in the National Institutes of Health Stroke Scale (NIHSS) score within 24 hours and categorize etiologies of ND according to clinical reversibility. ND etiologies were considered non-reversible if such causes may have produced or extended any areas of ischemic neurologic injury due to temporary or permanent impairment in cerebral perfusion. Seventy-one of 350 ischemic stroke patients experienced ND. Over half (54.9%) of the patients who experienced ND did so within the 48 hours of last seen normal. The median time to ND for non-reversible causes was 1.5 days (IQR 0.9, 2.4 days) versus 2.6 days for reversible causes (IQR 1.4, 5.5 days, p=0.011). After adjusting for NIHSS and hematocrit on admission, the log-normal survival model demonstrated that for each 1-year increase in a patient's age, we expect a 3.9% shorter time to ND (p=0.0257). In addition, adjusting for age and hematocrit on admission, we found that that for each 1-point increase in the admission NIHSS, we expect a 3.1% shorter time to ND (p=0.0034). We found that despite having similar stroke severity and age, patients with nonreversible causes of ND had significantly shorter median time to ND when compared to patients with reversible causes of ND.

Structural Integrity of the Contralesional Hemisphere Predicts Cognitive Impairment in Ischemic Stroke at Three Months

After stroke, white matter integrity can be affected both locally and distally to the primary lesion location. It has been shown that tract disruption in mirror’s regions of the contralateral hemisphere is associated with degree of functional impairment. Fourteen patients suffering right hemispheric focal stroke (S) and eighteen healthy controls (HC) underwent Diffusion Weighted Imaging (DWI) and neuropsychological assessment. The stroke patient group was divided into poor (SP; n = 8) and good (SG; n = 6) cognitive recovery groups according to their cognitive improvement from the acute phase (72 hours after stroke) to the subacute phase (3 months post-stroke). Whole-brain DWI data analysis was performed by computing Diffusion Tensor Imaging (DTI) followed by Tract Based Spatial Statistics (TBSS). Assessment of effects was obtained computing the correlation of the projections on TBSS skeleton of Fractional Anisotropy (FA) and Radial Diffusivity (RD) with cognitive test results. Significant decrease of FA was found only in right brain anatomical areas for the S group when compared to the HC group. Analyzed separately, stroke patients with poor cognitive recovery showed additional significant FA decrease in several left hemisphere regions; whereas SG patients showed significant decrease only in the left genu of corpus callosum when compared to the HC. For the SG group, whole brain analysis revealed significant correlation between the performance in the Semantic Fluency test and the FA in the right hemisphere as well as between the performance in the Grooved Pegboard Test (GPT) and theTrail Making Test-part A and the FA in the left hemisphere. For the SP group, correlation analysis revealed significant correlation between the performance in the GPT and the FA in the right hemisphere.

CD38 Exacerbates Focal Cytokine Production, Postischemic Inflammation and Brain Injury after Focal Cerebral Ischemia

BackgroundConverging evidence suggests that inflammatory processes significantly influence brain injury and clinical impairment in ischemic stroke. Although early studies suggested a key role of lymphocytes, recent data has emphasized the orchestrating function of innate immunity, i.e., macrophages and microglia. The bifunctional receptor and ectoenzyme CD38 synthesizes calcium-mobilizing second messengers (e.g., cyclic ADP-ribose), which have been shown to be necessary for activation and migration of myeloid immune cells. Therefore, we investigated the dynamics of CD38 in stroke and the impact of CD38-deficiency on cytokine production, inflammation and cerebral damage in a mouse model of cerebral ischemia-reperfusion.Methodology/Principal FindingsWe show that the local expression of the chemokine MCP-1 was attenuated in CD38-deficient mice compared with wildtype mice after focal cerebral ischemia and reperfusion. In contrast, no significant induction of MCP-1 expression was observed in peripheral blood after 6 hours. Flow cytometry analysis revealed less infiltrating macrophages and lymphocytes in the ischemic hemisphere of CD38-deficient mice, whereas the amount of resident microglia was unaltered. An up-regulation of CD38 expression was observed in macrophages and CD8+ cells after focal cerebral ischemia in wildtype mice, whereas CD38 expression was unchanged in microglia. Finally, we demonstrate that CD38-deficiency decreases the cerebral ischemic injury and the persistent neurological deficit after three days of reperfusion in this murine temporary middle cerebral artery occlusion (tMCAO) model.Conclusion/SignificanceCD38 is differentially regulated following stroke and its deficiency attenuates the postischemic chemokine production, the immune cell infiltration and the cerebral injury after temporary ischemia and reperfusion. Therefore CD38 might prove a therapeutic target in ischemic stroke.

The human Tp53 Arg72Pro polymorphism explains different functional prognosis in stroke

The functional outcome after stroke is unpredictable; it is not accurately predicted by clinical pictures upon hospital admission. The presence of apoptotic neurons in the ischemic penumbra and perihematoma area may account for poor prognosis, but whether the highly variable stroke outcome reflects differences in genetic susceptibility to apoptosis is elusive. The p53 tumor suppressor protein, an important transcriptional regulator of apoptosis, naturally occurs in humans in two variants with single nucleotide polymorphisms resulting in Arg or Pro at residue 72. We show that poor functional outcome after either ischemic or hemorrhagic stroke was linked to the Arg/Arg genotype. This genotype was also associated with early neurological deterioration in ischemic stroke and with increased residual cavity volume in intracerebral hemorrhage. In primary cultured neurons, Arg(72)-p53, but not Pro(72)-p53, interacted directly with mitochondrial Bcl-xL and activated the intrinsic apoptotic pathway, increasing vulnerability to ischemia-induced apoptotic cell death. These results suggest that the Tp53 Arg/Arg genotype governs neuronal vulnerability to apoptosis and can be considered as a genetic marker predicting poor functional outcome after stroke.