Stroke最新文献

Background: Activating glutamatergic neurons in the ipsilesional motor cortex can promote functional recovery after stroke. However, the underlying molecular mechanisms remain unclear. Clarifying key molecular mechanisms involved in recovery could help understand the development of neuromodulation strategies after stroke.

Methods: Adeno-associated virus 2/9-CamKIIa-hM3Dq-mCherry was injected into ipsilesional motor cortex by stereotaxic in the photothrombotic stroke model. Starting from the third day after the stroke, male mice were injected intraperitoneally with clozapine-N-oxide every day to activate excitatory neurons. C1q-blocking antibody and annexin V were used to inhibit C1q and exposed phosphatidylserine (EPS), respectively. The cylinder test and grid-walking test were performed to evaluate functional recovery. The potential molecular mechanisms of excitatory neuronal activation on microglia-mediated synaptic pruning after stroke by immunofluorescence, real-time polymerase chain reaction, Western blotting, and RNA sequencing.

Results: Activating excitatory neurons significantly promoted functional recovery and inhibited microglia-mediated synaptic pruning after stroke. Furthermore, it decreased EPS and C1q levels in synapses. On the contrary, inhibiting excitatory neurons aggravated functional defects, promoted microglia-mediated synaptic pruning, and increased EPS and C1q levels in synapses. Selective blocking of EPS repressed C1q tagging of synapses and microglia-mediated synaptic pruning and improved functional recovery. Meanwhile, blocking EPS markedly rescued synaptic density, and motor function deteriorated by chemogenetic inhibition. In addition, C1q-blocking antibody prevented phosphatidylserine engulfment by microglia.

Conclusions: Together, these data provide mechanistic insight into microglia-mediated synapse pruning after neuronal activation after stroke and identify the role of C1q binding to EPS in stroke treatment during the repair phase.

Background: Sex-specific differences in stroke risk factors, clinical presentation, and outcomes are well documented. However, little is known about real-world differences in transient ischemic attack (TIA) hospitalizations and outcomes between men and women.

Methods: This was a retrospective cohort study of the 2016 to 2021 Nationwide Readmissions Database in the United States. Adult patients hospitalized for TIA were included. Annual incidences of TIA hospitalizations for men and women were calculated using the US Census Bureau data. Primary end points were 90-day readmission for ischemic stroke or hemorrhage and compared between men and women. Demographics and comorbidities were captured and used to adjust for confounders using propensity score matching and logistic regression models.

Results: A total of 588 499 patients were identified; 326 794 (55.5%) were women. The estimated annual incidence of TIA hospitalizations was 42.4 (95% CI, 26.0-58.9) per 100 000 women and 36.2 (95% CI, 23.5-48.9) per 100 000 men (relative risk, 1.17 [95% CI, 1.13-1.21]; P<0.001). Overall, women were older, had higher rates of headache and psychiatric comorbidities, and had lower rates of vascular risk factors compared with men. Women were significantly less likely to be readmitted for ischemic stroke (hazard ratio, 0.86 [95% CI, 0.79-0.93]; P<0.001) and more likely to be readmitted for hemorrhage (hazard ratio, 1.12 [95% CI, 1.04-1.20]; P<0.001), with similar rates of antithrombotic use at the time of readmissions (P>0.05). Compared with ischemic stroke, hemorrhage readmissions were significantly associated with lower odds of home discharge (odds ratio, 0.83 [95% CI, 0.76-0.91]; P<0.001) and higher odds of death (odds ratio, 3.01 [95% CI, 2.35-3.87]; P<0.001).

Conclusions: Women have a higher incidence of TIA hospitalizations than men, which may be due to higher rates of nonischemic causes of transient neurological symptoms as evidenced by differences in baseline characteristics and lower rates of subsequent ischemic stroke. Future studies are needed to better characterize transient neurological symptoms in women to avoid excess hospitalizations and unnecessary treatments that may increase hemorrhage risk.

Background: The pathogenesis of spontaneous cervical artery dissection remains unclear, and no established predictors of recurrence exist. Our goal was to investigate the potential association between cervical artery tortuosity, a characteristic of patients with connective tissue disorder, and spontaneous cervical artery dissection.

Methods: The ReSect study (Risk Factors for Recurrent Cervical Artery Dissection) is an observational study that invited all spontaneous cervical artery dissection patients treated at the Innsbruck University Hospital between 1996 and 2018 for clinical and radiological follow-up. Internal carotid and vertebral artery tortuosity was assessed on magnetic resonance angiography using a validated 3-dimensional algorithm. Differences between patients and healthy controls as well as dependent on recurrence status were assessed by applying χ², Mann-Whitney U test, and Kruskal-Wallis test where applicable, and confounders were established by bivariable Pearson correlation. Logistic regression was used to address the impact of tortuosity on dissection occurrence and recurrence as well as its association to extracellular matrix proteome data derived from skin biopsies in a subset of patients.

Results: Magnetic resonance angiography was performed a median of 6.5 years after dissection in the included dissection patients. Patients with dissection (n=125) had significantly increased values of internal carotid artery tortuosity compared with healthy controls (n=24; odds ratio, 2.65 [95% CI, 1.68-3.86], 1 SD increase; P<0.01). This was also true for patients with long-term dissection recurrence (n=7) when compared with those with single time-point dissection (n=118; odds ratio, 2.00 [95% CI, 1.47-3.99], 1 SD increase; P<0.01). In patients with dissection and available extracellular matrix protein data (n=37), 6 of 13 (46.2%) proteins previously found linked with dissection recurrence were also associated with increased tortuosity. All 3 proteins associated with both anterior and posterior circulation tortuosity belonged to the desmosome-related cluster.

Conclusions: Internal carotid artery tortuosity is elevated in spontaneous cervical artery dissection patients compared with healthy controls, and this difference is most pronounced if individuals suffer from long-term dissection recurrence. Additionally, an association between tortuosity, being a readily measurable biomarker in routine magnetic resonance angiography, and proteomic markers of dissection recurrence exists, further enhancing the prospect of underlying subclinical connective tissue disease in dissection patients.

Background: The combined hormonal contraceptive (CHC) with ethinylestradiol and progestins is the most widely used contraceptive method among young women and is used by millions worldwide. However, uncertainties exist about the risk of ischemic stroke associated with the use of CHCs with low-dose ethinylestradiol (<50-µg ethinylestradiol) and with the newest fourth-generation progestins that have only been sparsely investigated for the risk of ischemic stroke.

Methods: In this cohort study based on Danish registries covering the entire Danish female population aged 18 to 49 years from 2004 to 2021, we investigated incidence rate ratios (IRRs) of ischemic stroke using CHCs compared with nonuse of hormonal contraceptives. Analyses focused on comparing CHCs based on ethinylestradiol content (30-40- versus ≤20-μg ethinylestradiol), progestin generation (second, third, and fourth) in CHCs, and route of administration (monophasic versus sequential). Poisson regression models adjusting for age, education, ethnicity, calendar year, and medication used for risk factors were utilized.

Results: In total, 1 711 757 nonpregnant women contributed 14 697 788 person-years to the investigation. For users of CHCs containing <50-µg ethinylestradiol, the adjusted IRR was increased by 1.77 (95% CI, 1.62-1.93) compared with nonusers of hormonal contraceptives. IRR did not differ between CHCs with 30- to 40- and ≤20-µg ethinylestradiol. Adjusted incidence rate difference between CHC users and nonusers of hormonal contraceptives ranged from 1 in 100 000 women per year in 18 to 24 years of age to 24 in 100 000 women per year in ≥45 years of age. Incidence rate in users of fourth-generation CHCs was 30% lower than that of second-generation CHCs adjusted IRR (0.70 [95% CI, 0.50-0.98]). IRR for users of third-generation CHCs did not differ significantly from that of second-generation users adjusted IRR (1.14 [95% CI, 0.97-1.35]).

Conclusions: Use of CHCs was associated with a 1.77 higher IRR of ischemic stroke. IRR did not relate to ethinylestradiol content in users of CHCs with <50-µg ethinylestradiol. IRR was 30% lower in users of fourth-generation than in users of second-generation CHCs.

Ischemic stroke is one of the leading causes of disability and mortality worldwide. Thrombosis is the main pathological process of stroke and is therefore an important therapeutic target in stroke prevention. In recent years, with the development of endovascular treatment and therefore retrieving the thrombus for further investigation, evidence is accumulating that immune cells are inextricably linked to stroke pathogenesis. Circulating immune cells have been found to induce immunothrombosis, and they actively participate in the formation of the thrombus by promoting platelet recruitment and thrombin activation. Additionally, the formation of thromboinflammation leads to increased instability of atherosclerotic plaques. We review the concepts of stroke immunothrombosis and thromboinflammation and the effect of immune cells on vessel recanalization and patient outcome. In addition, we elaborate on the possible mechanism of immune cells being activated and participating in thrombosis in ischemic stroke.

Background: Long-term patterns of functional outcome after intracerebral hemorrhage (ICH) have not been well elucidated in population-based studies from low- and middle-income countries. The aim of this study was to define long-term functional outcomes, associated prognostic factors, and recovery patterns for patients with acute ICH.

Methods: We conducted a prospective population-based stroke incidence study in Ulaanbaatar, Mongolia, with prospective follow-up. Multiple overlapping strategies were used to prospectively ascertain all strokes over 2 years. Patients were followed up at 28, 90, and 365 days. Associated factors of unfavorable outcome (defined as modified Rankin Scale scores, 3-6) and death at 365 days were identified using separate binary logistic regressions. Recovery pattern in terms of the proportions of patients with favorable outcomes (defined as modified Rankin Scale scores, 0-2) as the outcome was analyzed over time at 28, 90, and 365 days using generalized estimating equations with baseline covariates.

Results: A total of 1172 first-ever ICH cases were registered. Among these patients, 625 (56.4% of available modified Rankin Scale) cases had died and 853 (77.0%) had an unfavorable outcome at 365 days. The proportion of favorable outcomes increased from 12.1% at day 28 to 17.4% at day 90 and then to 23.0% at 1 year. Multivariable analysis revealed that older age, low socioeconomic status, absence of hypertension, hospital admission, neurosurgical intervention, and ICH severity, side, and intraventricular extension were independently associated with death/unfavorable outcome 365 days post-ICH. Most of these factors were also associated with the recovery pattern.

Conclusions: The prognosis from ICH in low- and middle-income countries is dismal, with 56% of patients dead and 77% having an unfavorable functional outcome at 365 days, although there was a pattern of continuous recovery over this time period. These findings stress the importance of developing effective primary prevention and continuous active care for survivors to reduce the burden of ICH in low- and middle-income countries.

Currently, most acute ischemic stroke patients presenting with a large vessel occlusion are first evaluated at a nonthrombectomy-capable center before transfer to a comprehensive stroke center that performs thrombectomy. Interfacility transfer is a complex process that requires extensive coordination between the referring, transporting, and receiving facilities. As a result, long delays are common, contributing to poor clinical outcomes. In this review, we summarize the accumulating literature about the clinical as well as radiological-infarct growth, collateral change, arterial recanalization, and hemorrhagic transformation-changes during interfacility transfer for thrombectomy. Recent evidence shows that clinical/radiological changes during transfer are heterogeneous across patients and impact long-term functional outcomes, highlighting the urgent need to optimize care during this time window. We review some of the most promising therapeutic strategies-for example, penumbral protection to reduce infarct growth-that may improve clinical outcome in patients being transferred to thrombectomy-capable centers. Finally, we discuss key methodological considerations for designing clinical trials aimed at reducing infarct growth during transfer.

Background: Sparse information regarding the long-term risk of acute myocardial infarction (MI) following a transient ischemic attack (TIA) emphasizes further research to guide preventive strategies and risk stratification in patients with a TIA.

Methods: We conducted a nationwide cohort study to investigate the 5-year risk of MI and all-cause mortality in patients with a first-time TIA. Patients with a first-time TIA were identified in the Danish Stroke Registry (2013-2020), matched on age, sex, and calendar year (1:4) with the general population and (1:1) with patients with first-time ischemic stroke. The 5-year risks of MI and all-cause mortality were estimated by the Aalen-Johansen and Kaplan-Meier estimators. The groups were compared using Cox regression, while adjusting for cardiovascular comorbidities.

Results: We identified 21 743 patients with TIA, 86 972 matched individuals from the general population, and 21 743 matched control patients with ischemic stroke. Median age was 70 (25th to 75th percentile, 60-78) years; 52% were male. Comorbidity burden was the lowest in general population controls, intermediate in patients with TIA, and the highest in patients with ischemic stroke. The 5-year risk of MI was 2.0% in patients with TIA, 1.5% in the general population (P<0.001), and 2.2% in the ischemic stroke population (P<0.001). After adjustment, these differences in MI rate were similar (TIA versus general population; hazard ratio, 0.99 [95% CI, 0.98-1.02] and TIA versus ischemic stroke; hazard ratio, 0.99 [95% CI, 0.96-1.01]). The 5-year risk of mortality was 17.0% in patients with TIA compared with 14.0% in the general population (P<0.001) and 27.0% in ischemic stroke population (P<0.001). The differences in mortality persisted following adjustments for patients with TIA versus general population (hazard ratio, 1.25 [95% CI, 1.19-1.31]) and for patients with TIA versus ischemic stroke (hazard ratio, 0.43 [95% CI, 0.41-0.46]).

Conclusions: Patients with first-time TIA had a low 5-year incidence of MI, which was not significantly different from that of the general population and patients with first-time ischemic stroke after adjustments for comorbidities. However, patients with TIA had a 25% higher all-cause mortality rate than the general population, which was not readily explained by MI risk. Hence, the findings do not endorse the need to raise further awareness regarding MI in patients with TIA.