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  • Calcitonin Gene-related Peptid (CGRP) Expression in Hp2-2 Mice After Subarachnoid Hemorrhage (SAH) in Intracranial Structures

    Final Number:

    Tomas Garzon-Muvdi MD MS; Gustavo Pradilla MD; Robert Thomas Wicks BS, BA; Jacob Ruzevick BS; Lindsay Edwards MD; Matthew Bender; Juan A. Mejia MD; Rafael J. Tamargo MD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2011 Annual Meeting

    Introduction: Vasospasm is an important complication after aneurysmal SAH. CGRP treatment after SAH has been shown to prevent vasospasm in animal models. CGRP is a potent vasodilator when injected subcutaneously, it is released from nerve endings of the trigeminal nerve during migraine, and activation of its receptor, which involves adenylate cyclase, leads to vasodilation. Haptoglobin (Hp) 2-2 genotype predisposes to vasospasm after SAH but the relationship of CGRP levels to Hp genotype has not been investigated. In this study we determined the expression levels of CGRP in the brain of wild-type (Hp1-1) mice and compared them to those of transgenic Hp2-2 mice at baseline and after SAH.

    Methods: Hp1-1 (n=12) and Hp2-2 (n=12) mice were randomized to three different groups: 1) no intervention (baseline, n=4), 2)surgery without SAH (n=4), or surgery+SAH (n=4) and were euthanized 24 hours after SAH. Tissues of the olfactory-bulbs (OB), forebrain (FB), caudate/putamen (C/P), brainstem/basilar-artery (BS/BA), and cerebellum (CER) were collected for analysis using ELISA (Quantikine-mouse CGRP immunoassay, R&D systems, Minneapolis,MN).

    Results: Compared to baseline, whereas CGRP expression decreased after SAH in Hp2-2 mice in the BS/BA region, its expression increased after SAH in Hp1-1 mice. In the CER CGRP expression was similar at baseline and after surgery without SAH in Hp1-1 and Hp2-2 mice; expression remained unchanged after SAH in Hp1-1 animals but increased in Hp2-2 mice. In the FB, surgery + SAH increased expression of CGRP in both genotypes. In the C/P CGRP levels decrease in Hp1-1 and Hp2-2 mice after SAH.

    Conclusions: Changes in CGRP expression may contribute to vasospasm after SAH. Diverging changes in the expression of CGRP in the BS/BA and CER between Hp1-1 and Hp2-2 mice appear to contribute to the increased severity of vasospasm in Hp2-2 animals.

    Patient Care: Understanding the mechanism by which this neuropeptide affects vasospasm may lead to therapeutic advances for vasospasm.

    Learning Objectives: The main objective is to learn about changes in vasoactive neuropeptides that may affect vasospasm after subarachnoid hemorrhage.

    References: Satoh, M., Perkins, E., Kimura, H., Tang, J., Chun, Y., Heistad, D. D., and Zhang, J. H. (2002). Posttreatment with adenovirus-mediated gene transfer of calcitonin gene-related peptide to reverse cerebral vasospasm in dogs. J Neurosurg 97, 136-142.

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