HEAD INJURY CLINICAL AND LABORATORY RESEARCH CENTER

该提案寻求支持全面的临床和 头部损伤研究实验中心。 我们的首要 目的是评价静脉给药 超氧化物歧化酶或东莨菪碱改善发病率， 几个头部受伤的人的死亡率。 这种做法的理由是， 这种方法依赖于关键的实验室研究结果， 创伤性脑损伤与 破坏氧自由基，对大脑产生不利影响 血管和兴奋性神经递质的释放， 导致病理性激动剂-受体相互作用。 的 这些药物的疗效将在一个合作的三- 在弗吉尼亚医学院和 马里兰州紧急医疗服务系统研究所。 两组都将使用标准化的结局指标， 通过临床研究进行补充，旨在评估 脑血管损伤和脑功能使用非侵入性 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， 适合未来的治疗干预。 经裁定 关于氧气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，我们现在扩大 这些观察沿着新的调查路线。 可能的共同- 胆碱能毒蕈碱和谷氨酸NMDA受体的参与 将被探索。 与年龄相关的变化将被视为 内源性和外源性阿片肽的保护作用。 血脑屏障状态改变的相互作用 因为血管损伤的其他促成形式将是 评估。 最后，潜在的增加释放的 兴奋性递质有助于自由基的形成， 探讨了 拟议实验室研究的目标将 进一步补充试验，因此，将继续我们的 强大的临床和实验室的长期传统 互动 通过实现这些目标，我们感到 相信我们将能够改善患者的预后， 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.