Gender Differences in Dopamine Function after TBI

描述(申请人提供)：创伤性脑损伤是一种 在美国流行，幸存者经常有几十年的 生产性寿命损失。据估计，目前有530万美国人与 因脑外伤导致的残疾。尽管有大约25%的人 脑外伤患者以女性为主，临床和动物占绝大多数 到目前为止，关于脑外伤的研究一直是在男性中进行的。有证据表明，女性有 颅脑损伤后出现脑震荡后症状的困难和较差的预后 与雄性相比。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，并在 颅脑损伤后DA系统功能被认为影响认知功能恢复。 众所周知，雌激素在多巴胺能功能中发挥着重要作用， 雌激素已被证明具有强烈的神经保护作用， TBI。然而，还没有人评估雌激素对DA功能的影响 以及从脑外伤中恢复认知能力。这项提案的目标是评估 雌激素对雌性啮齿动物多巴胺通路的影响 在TBI之后。哌醋甲酯对认知功能和多巴胺的影响 雌性和雄性啮齿动物在实验性脑损伤后的功能也将 学习。长期目标是阐明雌激素在DA系统中的作用。 中介认知缺陷，以开发和优化新的和现有的 专门针对和促进男性和女性康复的疗法 颅脑损伤后女性。

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.