Gender Differences in Dopamine Function after TBI

描述（由申请人提供）：创伤性脑损伤（TBI）是一种 在美国的流行病与幸存者往往有几十年的 生产性生命损失。据估计，目前有530万美国人生活在 TBI造成的残疾。尽管有25%的人 患有TBI的人群是女性，绝大多数临床和动物 迄今为止，对创伤性脑损伤的研究都是针对男性的。有证据表明， 脑震荡后症状更困难，TBI后结局更差 与男性相比。据推测，多巴胺I（DA）起着至关重要的作用 在工作记忆和执行功能的其他方面， TBI后DA系统功能被认为影响认知恢复。 众所周知，雌激素在多巴胺能功能中起重要作用， 雌激素已经被证明有神经保护作用， 创伤性脑损伤然而，没有人评估雌激素对DA功能的影响 和认知能力的恢复本提案的目的是评估 雌激素对雌性啮齿类动物与雄性啮齿类动物DA通路的影响 在TBI之后哌醋甲酯对认知操作和DA的影响 实验性TBI后雌性和雄性啮齿动物的功能也将被 研究了长期目标是阐明雌激素对DA系统的作用 介导的认知缺陷，以开发和优化新的和现有的 专门针对男性和女性的治疗， TBI后的女性

DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is an epidemic in the United States with survivors often having many decades of productive life loss. An estimated 5.3 million Americans currently live with disabilities resulting from TBI. Despite the fact that about 25% of the population with TBI are women, the large majority of clinical and animal research on TBI to date has been with males. Evidence shows that females have more difficulties with post-concussive symptoms and poorer outcome after TBI compared to males. It is suspected that dopamine I (DA) plays a crucial role in working memory and other aspects of executive functioning, and decreases in DA system function after TBI are thought to affect cognitive recovery. Estrogen is well known to play a significant role in dopaminergic functioning, and estrogen has been shown to have a neuroprotective effect acutely after TBI. However, no one has evaluated the effect of estrogen on DA functioning and cognitive recovery from TBI. The goal of this proposal is to evaluate the effects of estrogen on DA pathways in female rodents compared to male rodents after TBI. The effects of methylphenidate on cognitive performance and DA function in females and male rodents after experimental TBI will also be studied. The long-term goal is to delineate the role of estrogen on DA system mediated cognitive deficits in order to develop and optimize new and existing therapies that specifically target and enhance recovery of both males and females after TBI.