Alcohol exposure exacerbates inflammation and anxiety-like behavior induced by repeated mild TBI during adolescence

酒精暴露会加剧青春期期间反复轻度 TBI 引起的炎症和焦虑样行为

基本信息

批准号：
10605755
负责人：
Sydney M Vita
金额：
$ 6.72万
依托单位：
LSU HEALTH SCIENCES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-12-01 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10605755
关键词：
ARHGEF5 gene Address Adolescence Adolescent Adult Affect Alcohol consumption Alcohols Animal Model Animals Anti-Inflammatory Agents Anxiety Anxiety Disorders Area Astrocytes Automobile Driving Behavioral Brain Cause of Death Clinical Complex Development Environment Enzymes Event Exposure to Face Female Financial cost Funding General Population Growth and Development function Health Hippocampus (Brain)Human Immunohistochemistry Incidence Individual Inflammation Inflammation Mediators Inflammatory Inflammatory Response Injury Knowledge Lead Link Lipoxygenase Lipoxygenase Inhibitors Male Adolescents Measures Mentors Microglia Modeling Motion National Institute on Alcohol Abuse and Alcoholism Neurobiology Neurons Oral Outcome Outcome Measure Patient Self-Report Performance Persons Pharmaceutical Preparations Physiology Population Pre-Clinical Model Predisposition Prostaglandin-Endoperoxide Synthase Public Health Rattus Recording of previous events Reporting Research Role Series Sex Differences Signal Transduction Site Sports Testing Time Translating Traumatic Brain Injury United States Western Blotting Wistar Rats Work adolescent alcohol exposure alcohol exposure alcohol research alcohol response anxiety-like behavior axon injury base brain tissue chemokine clinically relevant comorbidity cytokine designer receptors exclusively activated by designer drugs disability high risk improved outcome inflammatory marker male mild traumatic brain injury neuroinflammation novel therapeutics peer preservation severe injury therapeutically effective tool

ARHGEF5 gene Address Adolescence Adolescent Adult Affect Alcohol consumption Alcohols Animal Model Animals Anti-Inflammatory Agents Anxiety Anxiety Disorders Area Astrocytes Automobile Driving Behavioral Brain Cause of Death Clinical Complex Development Environment Enzymes Event Exposure to Face Female Financial cost Funding General Population Growth and Development function Health Hippocampus (Brain)Human Immunohistochemistry Incidence Individual Inflammation Inflammation Mediators Inflammatory Inflammatory Response Injury Knowledge Lead Link Lipoxygenase Lipoxygenase Inhibitors Male Adolescents Measures Mentors Microglia Modeling Motion National Institute on Alcohol Abuse and Alcoholism Neurobiology Neurons Oral Outcome Outcome Measure Patient Self-Report Performance Persons Pharmaceutical Preparations Physiology Population Pre-Clinical Model Predisposition Prostaglandin-Endoperoxide Synthase Public Health Rattus Recording of previous events Reporting Research Role Series Sex Differences Signal Transduction Site Sports Testing Time Translating Traumatic Brain Injury United States Western Blotting Wistar Rats Work adolescent alcohol exposure alcohol exposure alcohol research alcohol response anxiety-like behavior axon injury base brain tissue chemokine clinically relevant comorbidity cytokine designer receptors exclusively activated by designer drugs disability high risk improved outcome inflammatory marker male mild traumatic brain injury neuroinflammation novel therapeutics peer preservation severe injury therapeutically effective tool

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项目摘要

ABSTRACT TBI is the leading cause of death and disability in people under 40 in the United States, with mild TBI (mTBI) being three times more common than moderate and severe injury combined. Currently, there are no effective therapeutics that will preserve or restore brain tissue and function after TBI. As a result, individuals may face a lifetime of deficits. Approximately one in five adolescents self-report having had one or more mild TBI (mTBI) with adolescent athletes being at a higher risk than non-athletic peers. Additionally, adolescents participating in team sports are more likely to take part in alcohol consumption. Both TBI and alcohol are known to cause neuroinflammation, which can be especially damaging to the developing, adolescent brain, including a higher incidence of anxiety reported following either of these insults independently. While mild TBI (mTBI) is the most common, research has shown that the effects of repeated mTBI (rmTBI) over time can build to a level of damage comparable to moderate or even severe injury. Additionally, studies have suggested that the inflammatory effects of TBI during development can lead to an exaggerated inflammatory response to alcohol. In this study, we propose to expose adolescent male and female rats to a series of four mTBIs interspersed with episodes of alcohol exposure to test the hypothesis that while rmTBI and alcohol exposure during adolescence both independently cause neuroinflammation, the combination of these insults will exacerbate this effect, and that this will translate to increases in anxiety-like behavior. Finally, we will treat these animals with the anti- inflammatory drug licofelone to investigate whether post-TBI neuroinflammation can be ameliorated, leading to an improvement in these outcomes.

抽象的 TBI是美国40岁以下人士的死亡和残疾的主要原因，轻度TBI （MTBI）比中度和重度损伤的三倍。目前，没有有效的治疗剂将保留或恢复TBI后脑组织和功能。结果，个人可能面对一生的赤字。大约五分之一的青少年自我报告具有一个或多个轻度TBI （MTBI）青春期运动员的风险高于非运动员同龄人。另外，青少年参加团队运动更有可能参加饮酒。 TBI和酒精都是已知的引起神经炎症，这可能对发展中的青春期大脑特别损害，包括在这两种侮辱中，焦虑发生率较高。虽然轻度TBI（MTBI）是最常见的是，研究表明，随着时间的推移，重复MTBI（RMTBI）的影响可以建立到损害可与中度甚至重度受伤相当。此外，研究表明发育过程中TBI的炎症作用会导致对酒精的炎症反应。在这项研究中，我们建议将青春期的雄性和雌性大鼠暴露于一系列散布的MTBIS中酒精暴露的发作以检验以下假设，即青春期期间rmtbi和酒精暴露两者都独立引起神经炎症，这些侮辱的组合将加剧这种影响，并且这将转化为焦虑般的行为的增加。最后，我们将用抗炎性药物licofelone研究是否可以改善TBI后神经炎症后，导致这些结果的改善。