Dissociation between vasospasm and functional improvement in a murine model of subarachnoid hemorrhage.

Published online

Journal Article

OBJECT: The efficacy of nimodipine was examined in a murine model of subarachnoid hemorrhage (SAH). End points included the diameter of the lumen of the middle cerebral artery (MCA) and behavioral outcome. An apolipoprotein E (apoE)-mimetic peptide, acetyl-AS-Aib-LRKL-Aib-KRLL-amide, previously shown to have promise in this model was tested both alone and in combination with nimodipine. The effects of carboxyamidotriazole (CAI), a non-voltage-gated calcium channel blocker, were explored using the same animal paradigm. METHODS: Experimental SAH was induced in male C57B1/6J mice. For 3 days postoperatively, behavioral analyses were performed. In the first experiment, the mice were treated with vehicle or with low- or high-dose CAI for 3 days. In the second experiment, the mice were treated with vehicle, high- and low-dose nimodipine, and/or the apoE-mimetic peptide. On postoperative Day 3 each mouse was killed and perfused. Following this, the right MCA was removed and its lumen measured. Mice that received nimodipine demonstrated significant behavioral improvements when compared with vehicle-treated mice, but there was no clear dose-dependent effect on MCA diameter. Administration of the apoE-mimetic peptide was associated with improved functional performance and a significant reduction in vasospasm. Mice that received high-dose CAI performed worse on functional tests, despite a significant increase in the diameters of their MCA lumina. CONCLUSIONS: These results demonstrate a dissociation between vasospasm and neurological outcomes that is consistent with findings of previous clinical trials.

Full Text

Duke Authors

Cited Authors

  • Mesis, RG; Wang, H; Lombard, FW; Yates, R; Vitek, MP; Borel, CO; Warner, DS; Laskowitz, DT

Published Date

  • September 15, 2006

Published In

Volume / Issue

  • 21 / 3

Start / End Page

  • E4 -

PubMed ID

  • 17029343

Pubmed Central ID

  • 17029343

Electronic International Standard Serial Number (EISSN)

  • 1092-0684

Digital Object Identifier (DOI)

  • 10.3171/foc.2006.21.3.4

Language

  • eng

Conference Location

  • United States