Intranasal delivery of calcitonin gene-related peptide reduces cerebral vasospasm in rats.
Cerebral vasospasm is the primary cause of sequelae and poor clinical conditions of subarachnoid hemorrhage (SAH); therefore, it is imperative to relieve vasospasm and improve cerebral blood supply. Calcitonin gene-related peptide (CGRP) is a potent vasodilator that is normally released by trigeminal sensory fibers but depleted following SAH. We propose that intranasal application may be an effective way to deliver CGRP to the brain and ameliorate vasospasm after SAH. In this study, we intranasally applied CGRP to rats and induced SAH by double-injection of autologous blood into the cisterna magna. Compared to intravenous injection, intranasal delivery led to a 10-fold higher level of CGRP in the brain. Intranasal CGRP significantly ameliorated vasospasm, improved cerebral blood flow, and reduced cortical and endothelial cell death. Moreover, CGRP increased the levels of vascular endothelial growth factor and stimulated angiogenesis. Altogether, our data demonstrate that intranasal CGRP delivery is a promising method for moderating vasospasm and reducing the associated ischemic brain injury after SAH in rats, and suggest that it may be a potential approach in clinic.
Department of Neurology, Key Laboratory of Cerebral Microcirculation, Universities of Shandong, Affiliated Hospital of Taishan Medical College, Taian, Shandong 271000, China. blsun88@163.com
Bao-liang
BL
Sun
Fa-ping
FP
Shen
Qing-jian
QJ
Wu
Shu-mei
SM
Chi
Ming-feng
MF
Yang
Hui
H
Yuan
Fang-min
FM
Xie
Yan-bo
YB
Zhang
Jun
J
Chen
Feng
F
Zhang
D000281:Administration, Intranasal; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage* / Q000627:therapeutic use; D017931:DNA Primers; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D020301:Vasospasm, Intracranial / Q000188:drug therapy*
D017931:DNA Primers; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D015740:Calcitonin Gene-Related Peptide