Background: Observational studies suggest an association between blood pressure (BP) and functional outcomes in ischemic stroke patients but whether this is causal or due to confounding is uncertain. We used Mendelian randomization (MR) to assess causality, and also explore whether particular classes of anti-hypertensives were associated with a better outcome after ischemic stroke. Methods: We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drugs from genome-wide association studies (GWAS) on 757,601 individuals. The primary outcome was 3-month dependence or death defined as a modified Rankin Scale (mRS) of 3-6. The secondary outcome was disability or death after 90 days defined as mRS 2-6. The Cochran’s Q statistic in the Inverse variance weighted (IVW) model, the weighted median, MR-Egger regression, leave-one-SNP-out analysis, MR-Pleiotropy Residual Sum and Outlier methods were adopted as sensitivity analyses. To validate our primary results, we performed independent repeat analyses and Bi-directional MR analyses. Results: Genetic predisposition to higher systolic and diastolic BP was associated with disability or death after ischemic stroke in univariable IVW MR analysis (OR=1.29, 95%CI 1.05-1.59, p=0.014; OR=1.27, 95%CI 1.07-1.51, p=0.006, respectively). Pulse pressure was associated with both dependence or death and disability or death after ischemic stroke (OR=1.05, 95%CI 1.02-1.08, p=0.002; OR=1.04, 95%CI 1.01-1.07, p=0.009, respectively). Angiotensin-converting enzyme inhibitor (ACEI) and calcium channel blocker (CCB) were significantly associated with improved functional outcomes (dependence or death, OR=0.76, 95%CI 0.62-0.94, p=0.009; OR=0.89, 95%CI 0.83-0.97, p=0.005). Proxies for β-blockers, angiotensin receptor blockers (ARB) and thiazides failed to show associations with functional outcomes (p>0.05). Conclusion: We provide evidence for an association of genetic predisposition to higher BP with a higher risk of 3-month functional dependence after ischemic stroke. Our findings support ACEI and CCB as promising antihypertensive drugs for improving functional outcomes in ischemic stroke.

The classification of microglial M1/M2 polarization in the acute phase of ischemic stroke remains controversial, which has limited further advances in neuroprotective strategy. To thoroughly assess the microglial phenotypes, we made the middle cerebral artery occlusion model in mice to simulate the acute pathological processes of ischemic stroke from normal conditions to acute cerebral ischemia and then to the early reperfusion period. The temporal changes in gene profiles, cell subtypes, and microglial function were comprehensively analyzed using single-cell RNA sequencing. We identified 37,614 microglial cells and divided them into eight distinct subpopulations. Mic_home, Mic_pre1, and Mic_pre2 subpopulations were three clusters mainly composed of cells from the control samples, in which Mic_home was a homeostatic subpopulation characterized by high expression of Hpgd and Tagap, and Mic_pre1 and Mic_pre2 were two clusters with preliminary inflammatory activation characteristics marked by P2ry13 and Wsb1 respectively. Mic_M1L1 and Mic_M1L2 subpopulations exhibited M1-like polarization manifested by the upregulation of inflammatory genes after ischemic stroke, while the intrinsic heterogeneity on the level of inflammatory responses and neurotrophic support properties was observed. Moreover, we identified three unique clusters of cells with low inflammation levels. Mic_np1, Mic_np2, and Mic_np3 were characterized by high expression of Arhgap45, Rgs10, and Pkm respectively. However, these cells did not show significant M2-like characteristics and their classic microglia function was also attenuated. These subpopulations exhibited higher activation of neuropeptide functional pathways. At last, we performed cell-cell communication analysis and identified major couplings contributing to the interaction between microglia and other cell populations. In summary, our study elucidated the temporal heterogeneity of microglia in the acute phase of ischemic stroke, which may facilitate the identification of effective neuroprotective targets to curb ischemic damage at an early stage.

PurposeThis study aimed at investigating a novel standby microwire technique to facilitate revascularization of large vessel occlusion due to underlying long-segment dissection.MethodsPatients with acute ischemic stroke with emergent large vessel occlusion (ELVO) due to underlying long-segment dissection were screened from the prospectively established database between January 2021 and May 2022. The clinical and radiological data of eligible patients who underwent endovascular treatment by using a standby microwire technique were investigated.ResultsOf the 165 acute ischemic stroke patients who underwent mechanical thrombectomy, the standby microwire technique was used in five patients aged 33–55 years old with occlusion due to underlying long-segment dissection. Of them, three patients were diagnosed with tandem lesions and three were located at the anterior circulation. A 300 cm exchange microwire was used as the standby microwire. Stent deployment was performed in all five patients. Groin puncture to reperfusion time ranged from 10–68 min. Technical success and favorable clinical outcomes were achieved in all five patients (100%). No technique-related complication was observed.ConclusionOur preliminary experience showed that the standby microwire technique was a useful ancillary approach to facilitate the revascularization of large vessel occlusion due to underlying long-segment dissection.

Background: Observational studies suggest a robust association between blood pressure (BP) and functional outcomes in ischemic stroke patients. We sought to identify novel associations of the genetic basis of 3-month functional outcome after ischemic stroke based on a Mendelian randomization (MR) framework.<break><break>Methods: We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drugs from genome-wide association studies (GWAS) on 757,601 individuals. The primary outcome was 3-month favorable functional outcome defined as modified Rankin Scale (mRS) of 0-2. The secondary outcome was excellent 90-day outcome defined as mRS 0-1. The Cochrans Q statistic in Inverse variance weighted (IVW) model, the weighted median, MR-Egger regression, leave-one-SNP-out analysis, MR-Pleiotropy Residual Sum and Outlier methods were adopted as sensitivity analyses. To validate our primary results, we performed independent repeat analyses and Bi-directional MR analyses.<break><break>Results: Genetic predisposition to higher systolic and diastolic BP was associated with a lower probability of 3-month excellent functional outcome after ischemic stroke in univariable IVW MR analysis (OR=1.29, 95%CI 1.05-1.59, p=0.014; OR=1.27, 95%CI 1.07-1.51, p=0.006, respectively). Pulse pressure was associated with both excellent and favorable functional outcome (OR=1.05, 95%CI 1.02-1.08, p=0.002; OR=1.04, 95%CI 1.01-1.07, p=0.009, respectively). Angiotensin-converting enzyme inhibitor (ACEI) and calcium channel blocker (CCB), were significantly associated with improved favorable functional outcome (OR=0.76, 95%CI 0.62-0.94, p=0.009; OR=0.89, 95%CI 0.83-0.97, p=0.005). Proxies for -blockers, angiotensin receptor blocker (ARB) and thiazides failed to show associations with functional outcome (p>0.05). <break><break>Conclusion: We provide evidence for a potential association of genetic predisposition to higher BP with higher risk of 3-month functional dependence after ischemic stroke. Our findings support ACEI and CCB as promising antihypertensive drugs for improving functional outcome in ischemic stroke.