OPIOIDS AND FLUID PERCUSSION BRAIN INJURY

本申请基于以下初步调查结果 新生猪的软脑膜小动脉收缩和脑血流和 液压冲击伤后脑组织代谢降低。这个 总体假设是阿片类药物导致了这种减少。 脑血流量与继发性脑缺血的关系 在这个模型中。为了检验这一假设，有三个具体目标 计划使用新生和幼年仔猪：1)表征 蛛网膜下腔局部血药浓度之间的关系 阿片类药物、脑血流动力学和液体后的氧合 损伤，2)确定关系的功能意义 脑内阿片类物质、脑氧合作用与脑组织 液体损伤后的循环，以及3)调查 内源性阿片类药物影响脑血管的机制 流体冲击损伤后的反应。血管反应 在这些实验中，将使用放射性微球进行测量 和闭合的颅窗准备。地方层面的阿片类药物和 脑脊液中的前列腺素将用 放射免疫分析。将获得脑氧合指数 使用近红外光谱分析。这些研究将探索 脑血流量调节机制的研究进展 新生猪的损伤模型，应提供新的信息 数据很少的区域。调查人员表示， 实验结果可能对脑出血的发病机制有临床意义。 头部受伤。

DESCRIPTION This application is based on preliminary findings that pial arterioles in newborn pigs constrict and cerebral blood flow and metabolism are decreased after fluid percussion injury in brain. The overall hypothesis is that opioids contribute to this reduction in cerebral blood flow and possibly to secondary cerebral ischemia in this model. To examine this hypothesis, three specific aims are planned using newborn and juvenile piglets: 1) to characterize the relationship between local periarachnoid concentrations of opioids, cerebral hemodynamics, and oxygenation following fluid injury, 2) to determine the functional significance of the relationship between brain opioids, brain oxygenation and the cerebral circulation following fluid injury, and 3) to investigate the mechanisms by which endogenous opioids affect cerebral vascular responses subsequent to fluid percussion injury. Vascular responses in these experiments will be measured using radioactive microspheres and a closed cranial window preparation. Local levels of opioids and prostanoids in cerebrospinal fluid will be measured using radioimmunoassay. An index of cerebral oxygenation will be obtained using near infrared spectroscopy. These studies will explore mechanisms involved in regulation of cerebral blood flow in a brain injury model in newborn pigs and should provide new information in an area where few data are available. The investigators suggest that experimental findings may have clinical relevance for mechanisms of head injury.