Inoue T, Shimizu H, Kaminuma T, Tajima M, Watabe K, Yoshimoto T
Department of Neurosurgery, Tohoku University School of Medicine, Sendai, Japan.
Neurosurgery. 1996 Nov;39(5):984-90. doi: 10.1097/00006123-199611000-00020.
The goal of this work was to investigate the efficacy of a calcitonin gene-related peptide (CGRP) slow-release tablet (CGRP tablet) for the prevention of cerebral vasospasm after subarachnoid hemorrhage (SAH).
Experimental SAH was produced in 10 cynomolgus monkeys by placing a clot around the internal carotid artery bifurcation (Day 0). In five animals, CGRP tablets (1200 micrograms of CGRP) were then placed in the cerebrospinal fluid space (CGRP group). In two animals, placebo tablets were similarly placed (placebo group). The remaining three animals were treated with no tablets after SAH (SAH group). A series of angiographic analyses were performed, before SAH and on Days 7 and 14, to examine changes in the diameters of the ipsilateral internal carotid artery, middle cerebral artery, and anterior cerebral artery. The CGRP concentration in the cerebrospinal fluid taken before each angiogram was also determined.
In the SAH and placebo groups, cerebral vasospasm developed on Day 7 (54.8% of the pre-SAH value at the internal carotid artery, 62.3% at the middle cerebral artery, 51.3% at the anterior cerebral artery, and 56.1% as an average of the three arteries). In the CGRP group, vasospasm was significantly ameliorated at the middle cerebral artery, at the anterior cerebral artery, and on average (81.7, 81.1, and 75.7%, P < 0.05, 0.03, and 0.02, respectively). The CGRP concentration was positive only on Day 7 for the CGRP group (6.5 nmol/L).
The CGRP tablet prevented cerebral vasospasm after SAH and may have significant potential for the treatment of patients with SAH.
本研究旨在探讨降钙素基因相关肽（CGRP）缓释片预防蛛网膜下腔出血（SAH）后脑血管痉挛的疗效。
通过在10只食蟹猴的颈内动脉分叉处放置血凝块制作实验性SAH（第0天）。然后，在5只动物的脑脊液腔隙中放置CGRP片（含1200微克CGRP）（CGRP组）。在2只动物中同样放置安慰剂片（安慰剂组）。其余3只动物在SAH后不放置任何片剂（SAH组）。在SAH前以及第7天和第14天进行一系列血管造影分析，以检查同侧颈内动脉、大脑中动脉和大脑前动脉直径的变化。同时还测定每次血管造影前采集的脑脊液中CGRP的浓度。
在SAH组和安慰剂组中，第7天出现了脑血管痉挛（颈内动脉为SAH前值的54.8%，大脑中动脉为62.3%，大脑前动脉为51.3%，三条动脉平均为56.1%）。在CGRP组中，大脑中动脉、大脑前动脉以及平均水平的血管痉挛均得到显著改善（分别为81.7%、81.1%和75.7%，P分别<0.05、0.03和0.02）。CGRP组仅在第7天CGRP浓度呈阳性（6.5纳摩尔/升）。
CGRP片可预防SAH后脑血管痉挛，对SAH患者的治疗可能具有显著潜力。
