Regulation of Cerebral Blood Flow After Traumatic Brain Injury

这项建议的总体假设是，创伤性脑损伤会导致脑血流(CBF)调节功能受损，从而在我们的颅脑损伤患者中产生一系列损伤，从明显的缺血到对二次损伤的易感性增加。在上一次拨款期间，我们评估了一种预防脑缺血的管理策略，方法是为大脑提供更高的灌流压力，以弥补受损大脑自动调节压力的能力受损。这项研究表明，我们可以显著减少二次损伤的发生，但更高的灌流压的其他后果(更多的成人呼吸窘迫综合征，可能加重脑水肿)抵消了减少缺血损伤的有益影响。这项研究的结果强调了拟议工作的重要性。这项拟议工作的总体目标是开发方法来识别那些面临二次损伤风险最大的患者，并开发一种通过纠正导致受损大脑对缺血损伤敏感的潜在血管异常来预防二次脑缺血的方法。第一个总体目标将通过研究颅脑损伤患者的CBF调节并确定这些测试的异常是否预示着更大的二次伤害风险(具体目标1-2)来实现。在研究结束时，我们计划确定在入院时可以进行的简单测试，以确定受到二次侮辱的风险更高的患者，因此谁将从CBF靶向治疗中受益最大。第二个目标将通过研究体内观察到的自我调节受损与离体血管的生肌反应的关系(特定目标#3)、通过研究各种血管活性物质与体内观察到的脑血流调节受损的关系(特定目标#3)以及通过研究L-精氨酸对脑血流量和脑血流调节的影响(特定目标#4)来实现。具体目的包括：1.建立重症监护病房脑血流调节的实用监测方法：2.研究颅脑损伤后脑血流调节受损的发生率和严重程度：3.研究脑挫伤后脑血流调节受损的原因：4.研究L精氨酸对脑外伤后局部或全脑缺血患者脑血流动力学的影响：

The overall hypothesis of this proposal is that traumatic brain injury causes impairment of cerebral blood flow (CBF) regulation that produces a spectrum of injury in our head injured patients, ranging from frank ischemia to increased susceptibility to secondary insults. During the last grant period, we valuated a management strategy to prevent ischemia by providing the brain with a higher perfusion pressure that would compensate for the impaired ability of the injured brain to pressure autoregulate. This study demonstrated that we could significantly reduce the occurrence of secondary insults, but other consequences of the higher perfusion pressure (more adult respiratory distress syndrome, possibly worsened cerebral edema) offset the beneficial effects of reducing ischemic insults. The results of this study emphasize the importance of the proposed works. The overall goals of the proposed work are to develop methods for identifying those patients who are at greatest risk of secondary insults and to develop a way to prevent secondary cerebral ischemia by correcting the underlying vascular abnormalities that cause the injured brain to be sensitive to ischemic insults. The first overall goal will be achieved by studying CBF regulation in head injured patients and determining if abnormalities on these tests predict a greater risk of secondary insults (Specific Aims #1-2). At the end of the study, we plan to have identified simple tests that can be performed on admission to identify patients at greater risk from secondary insults and who therefore would benefit most from CBF-targeted therapy. The second goal will be achieved by studying the relationship of the myogenic response in isolated vessels to the impairment of autoregulation observed in vivo (Specific Aim #3), by studying the relationship of various vasoactive mediators to the impairment of CBF regulation observed in vivo (Specific Aim #3), and by studying the effect of L-arginine on CBF and on CBF regulation (Specific Aim #4). The specific aims include: 1. To develop practical methods for monitoring CBF regulation in the intensive care unit: 2. To study the incidence and severity of impairment of CBF regulation after TBI: 3. To study the cause of impairment of CBF regulation after TBI: 4. To study the effect of L-arginine on cerebral hemodynamics in patients with regional or global ischemia (CBF<20 ml/100gm/min) after TBI: