The Role of Spreading Depolarizations in Concussion-like Injuries

每年约有380万人发生与运动相关的脑震荡。本病的诊断和治疗 伤害通常基于行为和认知缺陷，这些缺陷并不总是在接下来的时间里立即受到影响 一次受伤。脑震荡缺陷急性期的病理生理学基础尚不清楚，但可能 涉及一种称为扩展去极化(SD)的现象。十二烷基硫酸钠是一种传播很大的波 导致大脑活动严重但短暂的抑制的去极化。尽管SDS事件已经被 在对中度和重度创伤性脑损伤的背景下进行了数十年的研究，直到最近才发现 事件被认为发生在脑震荡中。这些观察和我们的初步数据提出了耐人寻味的 抑郁症可能是脑震荡的一些短期和长期后果的基础。.的存在 脑震荡期间的抑郁症需要验证，目前尚不清楚在脑震荡期间复发的抑郁症是否 脑震荡后的几个小时到几天会导致持续的认知缺陷。我们的长期合作 目标是改进脑震荡的诊断和治疗，并确定促进大脑恢复的策略 在脑震荡后进行修复。这项提案的目标是确定可持续发展战略是否有助于 脑震荡的症状，并确定第二次脑震荡在脑之前的有害影响 恢复。我的中心假设是抑郁是脑震荡的一个重要的潜在机制，它可以 使大脑容易受到第二次撞击和/或反复发作的抑郁的后续损害，导致短期 认知缺陷。这些研究的理由是，他们将直接测试SDS作为一种 脑震荡的潜在和有针对性的机制以及与脑震荡相关的长期缺陷。 SA1：将测试类似脑震荡的撞击引发抑郁的假设。SA2：测试撞击引发的假设 抑郁会导致CBF的短期和长期缺陷，使大脑容易受到随后的 冲击和破坏。SA3：将检验脑震荡样撞击会在 有意识和移动的动物以及短期的认知缺陷。

Approximately 3.8 million sports-related concussions occur each year. Diagnosis and treatment of these injuries is usually based on behavioral and cognitive deficits that are not always affected immediately following an injury. The pathophysiology underlying acute phases of concussion deficits are poorly understood but may involve a phenomenon termed spreading depolarization (SD). SDs are large propagating waves of complete depolarization that result in a profound but transient depression of brain activity. Although SDs events have been studied for decades in the context of moderate and severe traumatic brain injuries, only recently have these events been suggested to occur in concussion. These observations and our preliminary data raise the intriguing possibility that SDs underlie some of the short and long-term consequences of concussions. The presence of SDs during a concussion needs to be validated, and it is not yet known whether recurring SDs in the following hours to days following a concussion contributes to persistent cognitive deficits. Our long-term goal is to improve diagnosis and treatments for concussions and to identify strategies to enhance brain recovery and repair following a concussion. The objectives of this proposal are to determine whether SDs contribute to the symptoms of a concussion and identify the deleterious effects of a second concussion prior to brain recovery. My central hypothesis is that SDs are an important underlying mechanism of a concussion that can leave the brain susceptible to subsequent damage from a second impact and/or recurrent SDs resulting in short-term cognitive deficits. The rationale for these studies is that they will directly test the role of SDs as an underlying and targetable mechanism of concussions and the prolonged deficits associated with concussions. SA1: will test the hypothesis that concussion-like impacts initiate SDs. SA2: test the hypothesis that an impact-induced SDs will result in short and long-term deficits in CBF that renders the brain vulnerable to subsequent impacts and damage. SA3: will test the hypothesis that concussion-like impacts produce recurrent SDs in conscious and moving animals and short-term cognitive deficits.