CGRP IN SUBARACHNOID HEMORRHAGE

降钙素基因相关肽(CGRP)的体外释放 三叉神经感觉纤维是大脑中一种有效的血管扩张机制 发行量。对实验动物和患者的研究表明 蛛网膜下腔出血(SAH)后血管周围CGRP被耗尽。 蛛网膜下腔出血后CGRP耗竭提示一种重要的代偿性血管扩张剂 机制可能耗尽，这可能导致易感性 蛛网膜下腔出血后血管痉挛。这些研究的总体目标是获得 了解蛛网膜下腔出血后CGRP的调节和作用。第一 主要目的是确定控制CGRP水平的分子机制 在SAH后的三叉神经细胞中。建议进行研究，以测试 假设血管周围CGRP的长期枯竭是由于 抑制CGRP的生物合成。降钙素基因相关肽和mRNA水平 在三叉神经节细胞体中测量，并与 CGRP启动子的活性。大鼠三叉神经细胞启动子活性的研究 活体将使用腺病毒β-半乳糖苷酶报告进行测量 向量。这个项目的第二个主要目标是探索一部小说 预防蛛网膜下腔出血后血管痉挛的治疗方法血管痉挛是一种常见的 SAH的破坏性并发症，以及各种治疗方法 都失败了。CGRP是基因治疗的合理候选者，因为 蛛网膜下腔出血后对CGRP的血管扩张反应被保留或增强 相比之下，对其他几种脑血管扩张剂的反应减弱。 有人建议进行研究，以检验CGRP基因转移可以 蛛网膜下腔出血后恢复脑血管功能。我们将进行一些实验 一种新型的带血管环腺病毒载体的体外应用 SAH后的准备和体内实验。这个项目汇集了 具有脑循环和CGRP基因专业知识的研究人员 监管。深入了解CGRP基因表达的调控可能有助于 预防脑血管痉挛的治疗方法，包括基因疗法 在SAH之后。

DESCRIPTION Release of calcitonin gene-related peptide (CGRP) from trigeminal sensory fibers is a potent vasodilator mechanism in the cerebral circulation. Studies in experimental animals and patients have demonstrated that perivascular CGRP is depleted after subarachnoid hemorrhage (SAH). CGRP depletion after SAH suggests that an important compensatory vasodilator mechanism may be exhausted, which may contribute to susceptibility to vasospasm after SAH. The overall objective of these studies is to obtain insight into the regulation and function of CGRP following SAH. The first major goal is to identify the molecular mechanisms that control CGRP levels in trigeminal neurons following SAH. Studies are proposed to test the hypothesis that long-term depletion of perivascular CGRP is due to an inhibition of CGRP biosynthesis. CGRP peptide and mRNA levels will be measured in trigeminal ganglia cell bodies, and related to changes in the activity of the CGRP promoter. Promoter activity in trigeminal neurons in vivo will be measured using an adenoviral beta-galactosidase reporter vector. The second major goal of this project is to explore a novel therapeutic approach to prevent vasospasm after SAH. Vasospasm is a common and devastating complication of SAH, and a variety of therapeutic approaches have failed. CGRP is a reasonable candidate for gene therapy since vasodilator responses to CGRP are preserved or enhanced after SAH, in contrast to diminished responses to several other cerebral vasodilators. Studies are proposed to test the hypothesis that CGRP gene transfer can restore cerebral vascular function after SAH. Experiments will be performed using a novel adenoviral vector both in vitro with vascular ring preparations and in vivo following SAH. This project brings together investigators with expertise in cerebral circulation and CGRP gene regulation. Insight into regulation of CGRP gene expression may facilitate treatment, including gene therapy, for prevention of cerebral vasospasm after SAH.