Open Access
Intranasal delivery of calcitonin gene-related peptide reduces cerebral vasospasm in rats
Bao-liang Sun1,Fa-ping Shen1,Qing-jian Wu1,Shu-mei Chi1,Ming-feng Yang1,Hui Yuan1,Fang-min Xie1,Yan-bo Zhang1,Jun Chen1,Feng Zhang1
Department of Neurology, Key Laboratory of Cerebral Microcirculation, Universities of Shandong, Affiliated Hospital of Taishan Medical College, Taian, Shandong 271000, China.
DOI: 10.2741/E209 Volume 2 Issue 4, pp.1502-1513
Published: 01 June 2010

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.

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Bao-liang Sun, Fa-ping Shen, Qing-jian Wu, Shu-mei Chi, Ming-feng Yang, Hui Yuan, Fang-min Xie, Yan-bo Zhang, Jun Chen, Feng Zhang. Intranasal delivery of calcitonin gene-related peptide reduces cerebral vasospasm in rats. Frontiers in Bioscience-Elite. 2010. 2(4); 1502-1513.