Light Alcohol Consumption and Ischemic Stroke

少量饮酒与缺血性中风

• 批准号: 9028247
• 负责人: Hong Sun
• 金额: $ 32.63万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9028247
• 关键词: Address; Alcohol consumption; Alcohols; American; Apoptosis; Attenuated; Brain Injuries; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cerebral Ischemia; Cerebral cortex; Chronic; DNA Fragmentation; Doctor of Philosophy; Dose; Equilibrium; Gene Targeting; Genes; Genetic Suppression; Glucose; Goals; Human; Incidence; Individual; Inflammation; Inflammatory; Inflammatory Response; Ischemic Stroke; Ligands; Light; Mediating; Middle Cerebral Artery Occlusion; Mitochondria; Modeling; Molecular; Mus; Nerve Degeneration; Neuraxis; Neurons; Nuclear; Oxygen; PPAR gamma; Prevention; Prostaglandin D2; Rattus; Reactive Oxygen Species; Reperfusion Injury; Reperfusion Therapy; Risk; Risk Factors; Role; SOD2 gene; Signal Transduction; Testing; The Sun; Translating; Up-Regulation; Vascular Endothelial Cell; Weight; alcohol exposure; base; brain endothelial cell; deprivation; disability; drinking; feeding; improved; light effects; man; neuron apoptosis; neuroprotection; novel strategies; outcome forecast; public health relevance

 DESCRIPTION (provided by applicant): Transient focal cerebral ischemia is one of the most common types of ischemic stroke. Efforts to screen for agents/mechanisms that protect against cerebral ischemia/reperfusion (I/R) injury have not produced promising results. Interestingly, chronic heavy alcohol consumption increases the risk of ischemic stroke and produces neurodegeneration, whereas light alcohol consumption (LAC) decreases the risk of ischemic stroke and is neuroprotective. The present application will focus on identifying the cellular mechanisms of neuroprotection by LAC. Our aim is to translate these findings to humans suffering from the consequences of ischemic stroke. In our preliminary studies, we found that the neuroprotective effect of LAC appeared to be related to an increase in nuclear peroxisome proliferator-activated receptor gamma (PPARγ). We also found that LAC significantly attenuated transient focal cerebral ischemia-induced expression of inflammatory genes and DNA fragmentation. Further, lipocalin-type prostaglandin D2 synthase (L-PGDS) and manganese superoxide dismutase (MnSOD) were found to be upregulated in cerebral cortex by LAC. Based on these findings, our central hypothesis is that LAC protects against cerebral I/R injury by upregulating MnSOD via L-PGDS-mediated PPARγ activation. In specific aim #1, we propose to test the hypothesis that LAC attenuates vascular endothelial cell (VEC) inflammation and neuronal apoptosis following transient focal cerebral ischemia via an upregulated MnSOD. In specific aim #2, we propose to test the hypothesis that LAC attenuates VEC inflammation and neuronal apoptosis following transient focal cerebral ischemia via PPARγ-mediated MnSOD upregulation. In specific aim #3, we propose to test the hypothesis that LAC upregulates MnSOD and attenuates VEC inflammation and neuronal apoptosis following transient focal cerebral ischemia via L-PGDS-mediated PPARγ 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.