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.

摘要 女性占每年创伤性脑损伤(TBI)病例的41%。此外，当伤害率为 相比之下，女性的TBI与男性相同或高于男性，这表明女性具有独特的脆弱性。在……里面 此外，在过去的十年中，发病率和住院率都显著增加。 女性和越来越多的女性很可能归因于对格斗和碰撞运动的参与增加 和军队招生。尽管受伤人数很多，但对可能导致受伤的因素的研究很少。 使女性更容易受到伤害和她们所经历的特定症状的影响。今年5月 部分原因是普遍认为女性生殖激素对脑外伤具有神经保护作用。 临床前的研究有力地表明，女性在受伤后会有更好的结果，尽管 当注意适当地将数据正常化时，女性的结果通常与 男性。在临床上，研究显示了相互矛盾的结果，差异可能是由于时间点的选择 以及使用的结果衡量标准没有考虑生物、心理和社会方面以及基于性别的期望。 虽然损伤前的生殖激素水平一直很受关注，但很少有研究关注 女性受伤后的性激素。脑外伤后激素紊乱是一种公认的现象 而且很可能对复苏和结果起到很大作用。不太确定的是，这些监管的变化是如何 荷尔蒙可能会影响特定性别的症状，包括疼痛和情感障碍。神经可塑性， 情绪和学习与月经周期阶段和荷尔蒙模式紊乱呈负相关 影响这些领域。临床前的研究表明，压力和性激素都会受到剧烈干扰， 在脑损伤后长期发作。我们的工作显示出大脑代谢紊乱和异常变化的证据 在情感和伤害性行为上。这项提议的中心前提是女性性行为- 荷尔蒙(1)在损伤时调节大脑新陈代谢，导致最初的损伤 严重程度和(2)女性性激素的调节和产生的变化 负责受伤后症状学上的性别差异。目前提议的目标将是 确定伤害前和伤害后的变量和机制，使女性更容易受到1)和2)脑外伤的影响 与男性相比，恢复时间更长，结果也不同。这些目标的研究成果是 对于了解基于性别的差异，以制定针对性别的治疗干预措施至关重要。