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Sex differences in the effects of prior social isolation stress on stroke outcomes

先前的社会孤立压力对卒中结果影响的性别差异

基本信息

批准号：
10752478
负责人：
Macy Zardeneta
金额：
$ 3.63万
依托单位：
TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2028-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10752478
关键词：
Acute Acute Disease Adhesives Adult Affect Age Animals Area Astrocytes Awareness Biological Biological Assay Blood Blood - brain barrier anatomy Brain Brain Infarction CCL3 gene COVID-19 COVID-19 pandemic Cardiovascular Diseases Cardiovascular system Cause of Death Cell Line Cells Central Nervous System Cessation of life Chronic Disease Data Dementia Dextrans Disease Dose Endothelin-1 Excision Family Family member Female Flow Cytometry Fluorescein-5-isothiocyanate Forelimb Future General Population Goals Histologic Histology Hour Housing Human Immune Impaired cognition Incidence Infarction Inflammation Inflammatory Injury Intravenous Ischemic Stroke Label Learning Long-Term Effects Magnetic Resonance Imaging Matrix Metalloproteinases Measurement Measures Mediating Memory Microglia Minocycline Mission Modeling National Institute of Neurological Disorders and Stroke Nervous System Neurology Obesity Occupational Therapy Outcome Patient Isolation Patients Perfusion Persons Phagocytosis Pharmaceutical Preparations Phase Physical therapy Physicians Physiological Population Procedures Process Proteins Protocols documentation RANTES Rattus Recovery Research Risk Scientist Serum Severities Sex Differences Social Distance Social Network Social isolation Stress Stroke Survivors TLR4 gene Techniques Testing Tight Junctions Training Vibrissae Weight Work blood-brain barrier permeabilization brain health clinically relevant cytokine dementia risk experience glial activation inhibitor intraperitoneal language impairment male middle age mortality mortality risk nervous system disorder neuroinflammation novel object recognition physical process post stroke post stroke cognitive impairment sex social stressor stroke model stroke outcome stroke patient therapeutic target vasoconstriction

项目摘要

Project Summary Social isolation increases risk of all-cause mortality and chronic diseases such as obesity, cardiovascular disease, dementia, and stroke.12,13 A lack of social connectedness, or isolation, is exacerbated with age due to partner loss, family disconnect, and a narrowing of social networks. However, with the ongoing COVID-19 pandemic and long periods of social distancing, social isolation has become a widespread phenomenon. As such, it is urgent to elucidate the physiological effects of social isolation (SI) and subsequent vulnerability to injury or disease. Stroke is a leading cause of death worldwide and is the cause of 1 in 6 cardiovascular related deaths. Ischemic stroke accounts for over 80% of overall incidence.14,15 Social isolation after stroke is of clinical relevance due to the recovery process requiring patients to spend many hours in physical and occupational therapies away from family members, loss of mobility, and language impairment. Thus while social isolation in stroke patients has often been studied during the recovery period,16,17 a recent study showed that the risk of death due to stroke was higher when comparing the most isolated patients to the least isolated patients prior to stroke.18 In the following proposed studies the overarching hypothesis that prior-social isolation (SI) mediates worsened stroke outcomes will be tested. The immediate goal is to identify, if any, sex differences in prior-SI and stroke severity. The long-term goal is to understand the mechanism by which prior-SI affects stroke severity and propose a potential therapy for mitigating harmful effects of prior-SI. This will be studied in the following 3 aims: Aim 1: To investigate the effect of pre-stroke social isolation on stroke severity and outcome. -Sub-Aim 1a: To investigate the hypothesis that prior-SIS worsens acute post-stroke outcomes. -Sub-Aim 1b: To investigate the hypothesis that prior SIS worsens post-stroke cognitive impairment. Aim 2: To test the hypothesis that stroke outcomes are exacerbated by prior social isolation stress (SIS) due to maladaptive cellular changes and inflammation in the central nervous system. -Sub Aim 2a: To test the hypothesis that prior-SIS increases stroke-induced blood brain barrier permeability. -Sub Aim 2b: To test the hypothesis that prior-SIS will induce a neuroinflammatory state in which microglia and astrocytes become activated, leading to worsened stroke outcomes. Considering the extensive isolation undergone by the majority of the population throughout the COVID-19 pandemic, it is critical to consider the long-term effects of prior-SIS on stroke. These findings advance our understanding and awareness of the future implications of COVID-19. This training plan's focus on elucidating the effects of stressors on brain health and vulnerability to disease fit well with my goal of becoming a physician scientist in the field of neurology. The procedures described in this application are well established in the sponsor's lab, and the pilot data was acquired by me while learning these techniques.

项目总结