Prevention of cerebral vasospasm by calcitonin gene-related peptide slow-release tablet after subarachnoid hemorrhage in monkeys

OBJECTIVE: 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). METHODS: 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 mu g of CGRP) were then placed in the cerebrospinal fluid space (CCRP 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. RESULTS: 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 CCRP 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 CCRP concentration was positive only on Day 7 for the CGRP group (6.5 nmol/L). CONCLUSION: The CCRP tablet prevented cerebral vasospasm after SAH and may have significant potential for the treatment of patients with SAH.