Light Alcohol Consumption and Ischemic Stroke

Hong Sun，MD，PhD 项目总结/摘要 缺血性中风是脑卒中的主要原因之一， 死亡和终身残疾，并没有产生有希望的结果。有趣的是， 消费（LAC）降低缺血性中风的发生率并改善预后。最 最近，我们发现LAC在基础状态下促进脑血管新生和神经发生， 条件和缺血性卒中后。此更新应用程序将继续识别 LAC神经保护作用的细胞机制。我们的目标是翻译这些 这些发现适用于具有风险因素和患有缺血性中风后果的人。 在上一个资助期，我们进一步发现LAC上调脂质运载蛋白型前列腺素 D2合酶（L-PGDS），过氧化物酶体增殖物激活受体γ（PPARg），血管 内皮生长因子A（VEGF-A）和血管内皮生长因子受体2 （VEGFR 2）在大脑中。在初步研究中，LAC诱导的脑血管生成似乎 与L-PGDS增加有关。基于这些发现，我们的中心假设是， LAC通过上调VEGF-A/VEGFR 2促进脑血管生成和神经发生 L-PGDS介导的PPARg活化。在具体目标#1中，我们建议检验以下假设： LAC通过上调VEGF-A和VEGFR 2促进脑血管生成和神经发生。 在具体目标#2中，我们提出检验LAC促进脑血管生成的假设 以及通过PPARg介导的VEGF-A和VEGFR 2的上调的神经发生。具体目标 #3，我们提出检验LAC上调VEGF-A和VEGFR 2的假设， 通过L-PGDS介导的PPARg激活促进脑血管生成和神经发生。 这些研究的结果将产生深远的影响，而不仅仅是对拉丁美洲和加勒比地区的影响。我们 我相信，通过确定LAC的保护性靶点，我们将能够将治疗应用于 在有缺血性中风风险的个体中操纵这些靶点。

Hong Sun, MD, PhD PROJECT SUMMARY/ABSTRACT Efforts to screen for agents that prevent and treat ischemic stroke, one of the leading causes of death and permanent disability, have not produced promising results. Interestingly, light alcohol consumption (LAC) lowers the incidence and improves the prognosis of ischemic stroke. Most recently, we found that LAC promotes cerebral angiogenesis and neurogenesis under basal conditions and following ischemic stroke. This renewal application will continue identifying the cellular mechanism underlying the neuroprotective effect of LAC. We aim to translate these findings to humans having risk factors and suffering from the consequences of ischemic stroke. In the previous grant period, we further found that LAC upregulates lipocalin-type prostaglandin D2 synthase (L-PGDS), peroxisome proliferator-activated receptor gamma (PPARg), vascular endothelial growth factor A (VEGF-A), and vascular endothelial growth factor receptor 2 (VEGFR2) in the brain. In preliminary studies, LAC-induced cerebral angiogenesis appeared to be related to an increase in L-PGDS. Based on these findings, our central hypothesis is that LAC promotes cerebral angiogenesis and neurogenesis by upregulating VEGF-A/VEGFR2 via L-PGDS-mediated PPARg activation. In specific aim #1, we propose to test the hypothesis that LAC promotes cerebral angiogenesis and neurogenesis via upregulated VEGF-A and VEGFR2. In specific aim #2, we propose to test the hypothesis that LAC promotes cerebral angiogenesis and neurogenesis via PPARg-mediated upregulation of VEGF-A and VEGFR2. In specific aim #3, we propose to test the hypothesis that LAC upregulates VEGF-A and VEGFR2 and promotes cerebral angiogenesis and neurogenesis via L-PGDS-mediated PPARg activation. The findings from these studies will have far-reaching implications, beyond that for LAC. We believe that by identifying the protective targets of LAC we will be able to apply therapy to manipulate these targets in individuals at risk for ischemic stroke.