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Cerebral Mechanisms of Vulnerability Following Female Traumatic Brain Injury

女性脑外伤后易受伤害的大脑机制

基本信息

批准号：
10612425
负责人：
Tiffany Greco
金额：
$ 35.77万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10612425
关键词：
Acute Affect Affective Amenorrhea Anxiety Behavior Caring Cell Death Cerebrovascular Circulation Cerebrum Chronic Clinical Clinical Research Consensus Corticosterone Corticotropin-Releasing Hormone Coupling Data Data Analyses Data Reporting Development Drug Metabolic Detoxication Enrollment Enzymes Estradiol Estrogen Receptor beta Estrogens Estrus Etiology Excitatory Amino Acids Exclusion Female Free Radicals Functional disorder Gender Glycolysis Gonadal Steroid Hormones Hormonal Hormones Hospitalization Impairment Incidence Inflammation Injury Intervention Knowledge Learning Measurement Measures Mediating Menstrual cycle Mental Depression Metabolic Metabolism Military Personnel Mitochondria Monitor Mood Disorders Moods Neuronal Plasticity Nociception Norepinephrine Outcome Outcome Measure Oxidative Phosphorylation Pain Pain Disorder Pathway interactions Pattern Phase Physiological Play Predisposition Production Proestrus Quality of life Reactive Oxygen Species Recovery Regulation Research Role Secondary to Serotonin Severities Sex Differences Signal Transduction Stress Symptoms Therapeutic Intervention Time Traumatic Brain Injury Woman Work antagonist biopsychosocial chronic pain combat contact sports duloxetine expectation experience female sex hormone glucose metabolism glucose transport gray matter hormone regulation improved outcome inhibitor insight interest male men mortality negative affect neuronal circuitry neuroprotection neurotransmission novel pre-clinical preclinical study prevent reproductive hormone reuptake sex symptomatology targeted treatment timeline transmission process treatment strategy

项目摘要

ABSTRACT Females comprise 41% of annual cases of traumatic brain injury (TBI). Further, when the rate of injury is compared, female TBI is either the same or higher than males, indicating a unique vulnerability of females. In addition, rates of both incidence and hospitalization have significantly increased over the past decade in females and growing numbers are likely attributed to increased participation in combat and collision sports and military enrollment. Despite the high number of injuries, little has been done to study factors that may make females more susceptible to injury and the specific constellation of symptoms they experience. This may be due in part to the prevailing opinion that female reproductive hormones are neuroprotective against TBI. Pre-clinical work has strongly demonstrated that females have better outcomes following injury, although when care is taken to properly normalize data, females commonly have the same or worse outcomes than males. Clinically, studies have shown contradictory results and differences may be due to choice of timepoints and outcome measures used that do not consider biopsychosocial aspects and gender-based expectations. While pre-injury levels of reproductive hormones have been of interest, few studies have looked at the role of sex-hormones post-injury in females. Hormonal dysfunction following TBI is a well-established phenomenon and likely has a large role in recovery and outcome. Less established is how changes in regulation of these hormones may influence sex-specific symptomatology including pain and affective disorders. Neuroplasticity, mood and learning are associated with menstrual-cycle stage and disruptions in hormonal patterns negatively affect these domains. Pre-clinical work has shown that both stress and sex-hormones are disrupted acutely and chronically following TBI. Our work shows evidence of perturbed cerebral metabolism and abnormal changes in affective and nociceptive behaviors. The central premise of this proposal is that female sex- hormones (1) modulate cerebral metabolism at the time injury, contributing to initial injury severity and (2) changes in the regulation and production of female sex-hormones are responsible for sex-specific difference in symptomology post-injury. The current proposed aims will identify pre- and post-injury variables and mechanisms that make females more susceptible to 1) TBI and 2) prolonged recovery and differential outcomes compared to males. The research findings from these aims are critical to understanding sex-based differences to develop sex-specific therapeutic interventions.

摘要