DEVELOPMENT OF CALCITONIN-GENE-RELATED PEPTIDE SLOW-RELEASE TABLET IMPLANTED IN CSF SPACE FOR PREVENTION OF CEREBRAL VASOSPASM AFTER EXPERIMENTAL SUBARACHNOID HEMORRHAGE

The calcitonin gene-related peptide (CGRP), a known potent intrinsic c erebral vasodilator, is contained in the sensory nerves from trigemina l ganglia that inervate the cerebral arteries. We previously reported that human alpha CGRP (hCGRP) dilates spastic cerebral arteries after experimental subarachnoid haemorrhage (SAH) in rabbits. In the present study, we investigated the prophylactic potential of a sustained high er cerebrospinal fluid level of hCGRP against experimental cerebral va sospasm. An hCGRP slow-release tablet (hCGRP s-r tablet) was developed for cisternal implantation. Experimental SAH was induced by percutane ous cisternal injection of autologous arterial blood. Angiography was initiated on day I (before SAH) and performed everyday. The hCGRP s-r tablet was implanted into the cisterna magna on day 2 in the treated g roups. The spastic response of the basilar artery was maximized on day 4 in the non-treated (80.7% of day 1) and the placebo-treated (79.3%) groups. In contrast, the arterial diameters on day 4 were 96.1% and 9 0.5% of day 1 in the groups implanted with hCGRP 24 mu g and 153 mu g s-r tablets, respectively, We also measured the concentration of hCGRP in the cerebrospinal fluid (CSF) following implantation of the hCGRP 24 mu g s-r tablet in the cisterna magna. The hCGRP concentration befo re implantation was below the dectable level. Following implantation, the hCGRP level in the CSF was 23.12 nmol/L on the second day and rema ined at elevated levels until the fifth day. These experiments suggest that the intrathecal single implantation oi the hCGRP s-r tablet coul d product on elevated concentration of hCGRP in the CSF over five days and have prevented the cerebral vasospasm after SAH in the rabbit. Th e hCGRP s-r tablet may be clinically applicable in the treatment of pa tients with SAH against cerebral vasospasm.