Intranasal delivery of calcitonin gene-related peptide reduces cerebral vasospasm in rats.
Intranasal delivery of calcitonin gene-related peptide reduces cerebral vasospasm in rats.
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DOI：
10.2741/e209
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发表时间：
2010-06
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影响因子：
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通讯作者：
Baoliang 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
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文献类型：
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作者：
Baoliang 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
脑血管痉挛是蛛网膜下腔出血（SAH）的后遗症和临床条件差的主要原因；因此，缓解血管痉挛，改善脑供血是当务之急。降钙素基因相关肽（CGRP）是一种有效的血管舒张剂，通常由三叉神经感觉纤维释放，但在SAH后耗尽。我们认为鼻内应用CGRP可能是一种有效的将CGRP输送到大脑并改善SAH后血管痉挛的方法。在本研究中，我们给大鼠鼻内注射CGRP，并在大池内双注自体血诱导SAH。与静脉注射相比，鼻内给药导致大脑中CGRP水平高出10倍。鼻内CGRP可显著改善血管痉挛，改善脑血流，减少皮质细胞和内皮细胞死亡。此外，CGRP增加血管内皮生长因子水平，刺激血管生成。总之，我们的数据表明，经鼻给药CGRP是一种很有希望的方法，可以缓解大鼠SAH后的血管痉挛和减少相关的缺血性脑损伤，并提示它可能是一种潜在的临床方法。
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.