Anxious and Hyperactive Phenotype Following Brief Ischemic Episodes in Mice

Abstract

Poststroke emotional and behavioral abnormalities have an impact on outcome but have scarcely been characterized in animal models. We tested whether brief ischemic episodes induce behavioral changes in mice. 129/Sv mice were subjected to 30-min occlusion of left or right middle cerebral artery (MCAo) followed by reperfusion or sham operation (n = 9 or 10 per group). Eight to ten weeks later, mice were tested for spontaneous locomotor activity, anxiety in the elevated plus maze, and depressive behavior in the modified Porsolt forced swim test. Outcome was correlated to monoamine and amino acid levels and compared with histologic damage at 10 weeks. Ischemia was associated with increased activity (right MCAo) and anxiety (left MCAo), but not poststroke depression. Noradrenaline increased by 30%-45% in the ischemic striatum and correlated with locomotor activity (r = .48); dopamine and homovanillinic acid were decreased compared with sham. The lesion was confined to the striatum, and scattered neuronal death was observed in a number of remote brain regions. Brief ischemic episodes in the mouse induce an anxious, hyperactive but not depressive phenotype that may relate to left versus right hemispheric lesion location, alterations in brain monoamine levels, and selective neurodegeneration.