CGRP IN SUBARACHNOID HEMORRHAGE

描述降钙素基因相关肽（CGRP）从 三叉神经感觉纤维是大脑中有效的血管扩张机制， 流通 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耗尽。 SAH后CGRP耗竭表明，一种重要的代偿性血管扩张剂 机制可能已经用尽，这可能会导致对 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SAH后CGRP的调节和功能。 第一 主要目标是确定控制CGRP水平的分子机制 在SAH后三叉神经元中的作用 建议进行研究， 假设血管周围CGRP的长期消耗是由于 CGRP生物合成的抑制。 CGRP肽和mRNA水平将被 在三叉神经节细胞体中测量，并与 CGRP启动子的活性。 三叉神经元中的启动子活性 将使用腺病毒β-半乳糖苷酶报告基因进行体内测量 vector. 这个项目的第二个主要目标是探索一部小说 预防SAH后血管痉挛的治疗方法。 血管痉挛是一种常见的 和毁灭性的并发症，以及各种治疗方法 失败了 CGRP是基因治疗的合理候选者， SAH后CGRP的血管舒张反应保持或增强， 与对其他几种脑血管扩张剂的反应减弱形成对比。 提出了研究来验证CGRP基因转移可以 恢复SAH后的脑血管功能。 将进行实验 使用一种新的腺病毒载体， 制备和SAH后的体内研究。 该项目汇集了 具有脑循环和CGRP基因专业知识的研究人员 调控 深入了解CGRP基因表达的调控可能有助于 用于预防脑血管痉挛的治疗，包括基因治疗 SAH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.