HEAD INJURY CLINICAL AND LABORATORY RESEARCH CENTER

这项提案寻求对全面的临床和 头部损伤研究实验室中心。我们的初选 目的是评估静脉注射或静脉注射的疗效 超氧化物歧化酶或东莨菪碱在改善发病率和 几个头部受伤的人的死亡率。这样做的理由是 该方法依赖于关键的实验室保守党发现，这些发现表明 创伤性脑损伤与脑血管疾病的发生有关 破坏氧自由基，对大脑产生不利影响 血管系统与兴奋性神经递质的释放 有助于病理性激动剂-受体的相互作用。这个 这些药物的疗效将在合作的三个方面进行评估- ARM试验在弗吉尼亚医学院和 马里兰紧急医疗服务系统研究所。 两个小组都将使用标准化的结果衡量标准，并将 以临床研究为补充，旨在评估 无创检测脑血管损伤与脑功能 措施。 拟议的实验室研究将补充临床试验。 同时为这些机制提供新的见解，可能 服从于未来的治疗干预。在做出了 关于氧的破坏性后果的开创性观察 自由基和过度的神经递质释放，我们现在延长 这些观察沿着新的调查路线进行。可能的联合- 胆碱能M受体和谷氨酸NMDA受体的参与 将会被探索。与年龄相关的变化将被考虑为 内源性和外源性阿片肽的保护作用。 血脑屏障状态改变的交互作用 因为其他有助于血管妥协的形式将是 已评估。最后，增加释放的可能性 有助于自由基形成的兴奋性递质将是 探索过了。拟议实验室研究的目标将是 进一步补充审判，因此，将继续我们的 强大的临床和实验室的悠久传统 互动。通过这些目标的实现，我们感到 相信我们将有能力改善患者的预后 头部严重受伤。

This proposal seeks support for a comprehensive clinical and laboratory center for the study of head injury. Our primary objective is to evaluate the efficacy of either IV administered superoxidase dismutase or scopolamine in improving morbidity and mortality in several head-injury humans. The rationale of this approach rests upon key laboratory tory findings which indicate that traumatic brain injury is associated withth the generation of damaging oxygen radicals which adversely influence the cerebral vasculature and the release of excitatory neurotransmittter which contribute to pathologic agonist-receptor interactions. The efficacy of these drugs will be assessed in a collaborative three- arm trialhere at the Medical College of Virginia and at the Maryland Institute for Emergency Medical Services Systems. Standardized outcome measures will be used by both groups and will be complemented by clinical studies directed toward assessment of cerebrovascular damage and brain function using non-invasive measures. The proposed laboratory studies will complement the clinical trial while providing new insights into those mechanisms possibly amenable to future therapeutic intervention. Having made the seminal observations regarding the damaging consequences of oxygen radicals and excessive neurotransmitter release, we now extend these observations along new lines of inquiry. The possible co- involvement of cholinergic muscarinic and glutamate NMDA receptors will be explored. Age related changes will be considered as will the protective effect of endogenous and exogenous opioid peptides. The interactive role of altered bloodbrain barrier status as well as other contributing forms of vascular compromise will be evaluated. Lastly, the potential that the increased release of excitatory transmitters contributes to radical formation will be explored. The goals of the proposed laboratory studies will further complement the trial and thus, will continue our longstanding tradition of strong clinical and laboratory interaction. Through the accomplishment of these goals we feel confident that we will be capable of improving outcome in patients with severe head injury.