Cerebral Mechanisms of Vulnerability Following Female Traumatic Brain Injury

女性脑外伤后易受伤害的大脑机制

• 批准号: 10404605
• 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
• 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/10404605
• 关键词: Acute; Affect; Affective; Amenorrhea; Anxiety; Attenuated; 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; 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; Physiological; Play; 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; TimeLine; Traumatic Brain Injury; Woman; Work; antagonist; base; biopsychosocial; chronic pain; classical conditioning; combat; contact sports; duloxetine; expectation; experience; female sex hormone; glucose metabolism; glucose transport; gray matter; hormone regulation; improved outcome; inhibitor; injury recovery; insight; interest; male; men; mortality; negative affect; neuronal circuitry; neurotransmission; novel; pre-clinical; preclinical study; prevent; reproductive hormone; reuptake; sex; symptomatology; targeted treatment; transmission process; treatment strategy

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.

抽象的 女性占每年脑外伤（TBI）病例的41％。此外，当受伤率为 相比之下，女性TBI的相同或高于男性，表明女性的独特脆弱性。在 此外，在过去的十年中，发生率和住院的发生率都显着提高 女性和人数增长可能归因于参与战斗和碰撞运动的增加 和军事入学。尽管受伤数量很大，但研究因素可能几乎没有 使女性更容易受到伤害和症状的特定症状。这可能 部分原因是普遍认为女性生殖激素对TBI具有神经保护作用。 临床前的工作强烈证明，受伤后女性的结果更好，尽管 当小心地将数据正常化时，女性通常会有相同或更差的结果 男性。在临床上，研究表明结果矛盾，差异可能是由于时间点的选择 以及未考虑生物心理社会方面和基于性别的期望的结果指标。 尽管受伤前的生殖激素水平引起了人们的关注，但很少有研究研究的作用 女性的性激素伤后。 TBI之后的激素功能障碍是一种完善的现象 并且可能在恢复和结果中起着重要作用。较少成熟的是这些调节的变化如何 激素可能会影响性别特异性症状学，包括疼痛和情感障碍。神经塑性， 情绪和学习与月经周期阶段和激素模式的破坏有关 影响这些领域。临床前的工作表明，压力和性激素都受到急剧破坏，并且 长期跟随TBI。我们的工作显示出脑代谢和异常变化的证据 在情感和伤害性行为中。该提议的主要前提是女性性 - 激素（1）在损伤时调节大脑代谢，导致初始损伤 严重程度和（2）女性性激素的调节和产生的变化是 在伤害后负责特定性别的症状差异。当前提议的目标将 确定使女性更容易受到1）TBI和2的损害后变量和机制 与男性相比，长期恢复和差异结果。这些目标的研究结果是 对于理解基于性别的差异至关重要，以发展性别特定的治疗干预措施。