Nasal Administration Of Calcitonin Gene-Related Peptide Into Central Nervous System Protect Cerebral Vasospasm Following Subarachnoid Hemorrhage

OBJECTIVES:1.To investigate the effect of CGRP given intranasally on relief CVS following SAH.2.To investigate the effect and mechanism of CGRP given intranasally on new cerebral vessel generation after SAH.METHOD:1. In this study, adult male Wister rats were used as experimental animals. Cisterna injection twice of freshly autologous arterial blood was used to induce SAH in rats. The rats were divided into : normal control group, SAH group, per nasal NS SAH group, per nasal CGRP SAH group. Somatotype microscope and living body circulation measure system were used to observe the caliber of BA in 72h after second SAH ; To measure parietal cortex rCBF in before first SAH, in 1/2h, 1h, 6h, 12h after second SAH given intranasally by laser-Doppler flow meter, developmently observe regional cerebral blood floe of rats.2. The SAH model in rats was established , the rats were divided into : normal control group, SAH group, per nasal NS SAH group, per nasal CGRP SAH group. Rats were sacrificed at 72h after second SAH, the brain were taken out and made into the coronal frozen section. Immunohistochemical staining was used to detect the expression of CD31 and VEGF in cortex and hippocamp respectively; the expression of VEGF mRNA and the protein expression of VEGF in cortex and hippocamp of brain were assessed by technic of TR-PCR and West blot respectively.RESULT: 1.In 72h after second SAH, the BA in SAH group and NS SAH group obviously cramped, the caliber of BA was significantly coarctat compared with that in normal group (P<0.01); The BA in CGRP SAH group slighely cramped, the caliber of BA was lightly coarctat compared with that in SAH group and NS SAH group(P<0.01); the BA caliber of every group is 48.18% 47.69% 93.13% of normal group respectively. The rCBF in SAH group and NS SAH group was evidently degraged compared with normal group(P<0.01); the rCBF in CGRP SAH group was smally step down compared with SAH group and NS SAH group (P<0.01); The rCBF cut down after second SAH every group, nadir in 1h, did not obviously return within 12h.2. In 72h after second SAH, the expression of CD31, VEGF enhance respectively in cortex and hippocamp in SAH group and NS SAH group that have more macs cell compared with normal group(P<0.01); the expression of CD31, VEGF in cortex and hippocamp in CGRP SAH group that abound with immue masculin cell is the most obvious contrasted to SAH group and NS SAH group (P<0.01); the expression of VEGF mRNA and the protein expression of VEGF in cortex and hippocamp in SAH group and NS SAH group increased respectively, cnotrast with that in normal group (P<0.01); the expression of VEGF mRNA and the protein expression of VEGF in cortex and hippocamp in CGRP SAH group was the most maximun respectively, cnotrast with that in SAH group and NS SAH group (P<0.01).CONCLUSION:1.The CGRP via intranasal pathway can relieve BA vasospasm after SAH, increase rCBF, improve cerebral circulation, raise brain blood provision, play an important role in releasing CVS following SAH.2. The CGRP given intranaseny can stimulate CD31 expression in cortex and hippocamp, increase the density of new blood vessels, enhance the expression of VEGF cell VEGF mRNA VEGF protein, VEGF that can promote new blood generation is bloodvessel regulatory factor. Thus, the CGRP via intranasal pathway can promote new cerebral vessels generation, increase cerebral blood flow , improve cerebral circulation.