Multi-protein complexes called inflammasomes have recently been identified and shown to contribute to cell death in tissue injury. Intravenous immunoglobulin (IVIg) is an FDA-approved therapeutic modality used for various inflammatory diseases. The objective of this study is to investigate dynamic responses of the NLRP1 and NLRP3 inflammasomes in stroke and to determine whether the NLRP1 and NLRP3 inflammasomes can be targeted with IVIg for therapeutic intervention. Primary cortical neurons were subjected to glucose deprivation (GD), oxygen–glucose deprivation (OGD) or simulated ischemia-reperfusion (I/R). Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion. Neurological assessment was performed, brain tissue damage was quantified, and NLRP1 and NLRP3 inflammasome protein levels were evaluated. NLRP1 and NLRP3 inflammasome components were also analyzed in postmortem brain tissue samples from stroke patients. Ischemia-like conditions increased the levels of NLRP1 and NLRP3 inflammasome proteins, and IL-1β and IL-18, in primary cortical neurons. Similarly, levels of NLRP1 and NLRP3 inflammasome proteins, IL-1β and IL-18 were elevated in ipsilateral brain tissues of cerebral I/R mice and stroke patients. Caspase-1 inhibitor treatment protected cultured cortical neurons and brain cells in vivo in experimental stroke models. IVIg treatment protected neurons in experimental stroke models by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. Our findings provide evidence that the NLRP1 and NLRP3 inflammasomes have a major role in neuronal cell death and behavioral deficits in stroke. We also identified NLRP1 and NLRP3 inflammasome inhibition as a novel mechanism by which IVIg can protect brain cells against ischemic damage, suggesting a potential clinical benefit of therapeutic interventions that target inflammasome assembly and activity.

Background and Purpose-Pathogenetic classification of intracerebral hemorrhage (ICH), using systems such as SMASH-U (structural vascular lesions, medication, cerebral amyloid angiopathy [CAA], systemic disease, hypertension, or undetermined), is important in predicting functional outcomes and mortality in patients with ICH. This study aimed to compare pathogenetic subtypes between the first and recurrent ICH. Methods-This study obtained data related to 4578 consecutive acute patients with ICH from the National Taiwan University Hospital Stroke Registry during January 1995 to December 2013. Using the SMASH-U method, patients were classified into 6 subtypes. We then analyzed the outcomes of first-ever ICH cases and pathogenetic classification of recurrent ICH. Results-Among 3785 patients who experienced first-ever ICH (male, 63.3%; mean age, 58.7±17.0 years), the most common cause was hypertensive angiopathy (54.9%), followed by CAA (12.2%), systemic disease (12.1%), undetermined (10.1%), structural vascular lesions (7.8%), and medication related (2.9%). In 185 cases of recurrent ICH, pathogenetic differences between the 2 ICH events were observed in 34 (18.4%) cases, most of which were CAA to hypertensive angiopathy (n=10) or vice versa (n=7). The rates of ICH recurrence were highest for systemic disease-related and CAA-related ICH at 1, 5, 10, and 15 years after the indexed ICH event. Conclusions-In

BackgroundThe association between ischemic stroke and 2 single nucleotide polymorphisms (SNPs) on chromosome 12p13, rs12425791 and rs11833579 appears inconsistent across different samples. These SNPs are close to the ninjurin2 gene which may alter the risk of stroke by affecting brain response to ischemic injury. The purpose of this study was to investigate the association between these two SNPs and ischemic stroke risk, as well as prognostic outcomes in a Taiwanese sample.MethodsWe examined the relations of these two SNPs to the odds of new-onset ischemic stroke, ischemic stroke subtypes, and to the one year risk of stroke-related death or recurrent stroke following initial stroke in a case-control study. A total of 765 consecutive patients who had first-ever ischemic stroke were compared to 977 stroke-free, age-matched controls. SNPs were genotyped by Taqman fluorescent allelic discrimination assay. The association between ischemic stroke and SNPs were analyzed by multivariate logistic regression. Cox proportional hazard model was used to assess the effect of individual SNPs on stroke-related mortality or recurrent stroke.ResultsThere was no significant association between SNP rs12425791 and rs11833579 and ischemic stroke after multiple testing corrections. However, the marginal significant association was observed between SNP rs12425791 and large artery atherosclerosis under recessive model (OR, 2.30; 95%CI, 1.22-4.34; q-value = 0.062). Among the 765 ischemic stroke patients, 59 died or developed a recurrent stroke. After adjustment for age, sex, vascular risk factors and baseline stroke severity, Cox proportional hazard analysis indicated that the hazard ratios were 2.76 (95%CI, 1.34-5.68; q-value, 0.02) and 2.15 (95%CI, 1.15-4.02; q-value, 0.03) for individuals with homozygous variant allele of rs12425791 and rs11833579, respectively.ConclusionsThis is a precedent study that found genetic variants of rs12425791 and rs11833579 on chromosome 12p13 are independent predictors of stroke-related mortality or stroke recurrence in patients with incident ischemic stroke in Taiwan. Further study is needed to explore the details of the physiological function and the molecular mechanisms underlying the association of this genetic locus with ischemic stroke.

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Intracerebral hemorrhage patients with prior warfarin use, but not antiplatelet use, had significantly higher case fatality at 6 months.

The dispatchers should spend more time identifying stroke patients by following the dispatch protocol. Recognition of stroke by dispatchers was associated with improved stroke care.

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ObjectiveTo conduct a meta-analysis to evaluate the effect of endovascular therapy (EVT) in mild acute ischemic stroke (AIS) due to proximal versus distal occlusions.MethodsWe searched PubMed, Embase, the Cochrane Library, and clinicaltrials.gov from January 2000 to September 2021 to identify studies comparing EVT versus best medical management (BMM) in AIS with National Institutes of Health Stroke Scale (NIHSS) scores ≤5 due to proximal internal carotid artery (ICA) or M1 versus distal M2 occlusions. We included studies that reported the number of patients with proximal or distal occlusions separately and reported the number of patients with freedom of disability (modified Rankin Scale (mRS) score 0–1) or functional independence (mRS score 0–2) at 90 days in proximal or M2 occlusions, respectively. OR with 95% CI was used.ResultsWe identified six studies with 653 proximal ICA and M1 occlusion patients and 666 distal M2 occlusion patients. Pooled results showed EVT versus BMM was associated with a higher rate of being disability-free in patients with proximal occlusions (OR 1.58, 95% CI 1.09 to 2.30), but was associated with a lower rate of being disability-free in patients with M2 occlusions (OR 0.70, 95% CI 0.49 to 0.99). Effect of EVT in proximal versus distal occlusions was substantially different (P for interaction=0.002). A similar pattern was seen for functional independence (P for interaction=0.05).ConclusionsFor patients with mild AIS, observational data suggest that EVT may be beneficial for proximal ICA or M1 but not for distal M2 occlusions. Randomized trials are needed to confirm these findings.PROSPERO registration numberCRD42021281034.