• Rachel G Mesis, Haichen Wang, Frederick W Lombard, Robert Yates, Michael P Vitek, Cecil O Borel, David S Warner, and Daniel T Laskowitz.
• Multidisciplinary Neuroprotection Laboratories and the Department of Medicine (Neurology), Duke University Medical Center and Duke University School of Medicine, Durham, North Carolina, USA.
• Neurosurg Focus. 2006 Jan 1;21(3):E4.

ObjectThe 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.MethodsExperimental 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.ConclusionsThese results demonstrate a dissociation between vasospasm and neurological outcomes that is consistent with findings of previous clinical trials.

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