Hyperactive and anxious phenotype following brief ischemic episodes in mice

Post-stroke emotional and behavioural abnormalities include a wide range of emotional and cognitive disturbances and have significant impact on long-term outcome. In animals models of stroke however there is little evidence of possible behavioural correlates of such post-stroke neuropsychiatric conditions. Here, we tested whether mild focal brain ischemia induces long-term behavioural changes and neuropsychiatric outcome in mice. 129/SV wild-type mice were anesthetized with isofluorane and subjected to 30 min filamentous occlusion of the left or right middle cerebral artery (MCAo) followed by reperfusion or sham operation (n = 10 animals per group). Eight weeks after MCAo, animals were consecutively subjected to three behavioural tests, i.e. (1) spontaneous locomotor activity testing (day 56), (2) the elevated plus-maze (day 63 and (3) the modified Porsolt forced swim test (on day 70). We present evidence that mild cerebral ischemia is associated with increased spontaneous locomotor activity (right MCAo > left MCAo > sham) and with post-stroke anxiety (left MCA > right MCAo > sham), but we obtained no evidence of a post-stroke depressive phenotype. Noradrenaline levels were significantly increased by 30 – 45% in the ischemic striatum and significantly correlated with locomotor activity (r = 0.48) while the levels of dopamine and homovanillinic acid were decreased compared to sham operated animals. The ischemic lesion was confined to the ipsilateral striatum and scattered neuronal death was observed in a number of remote brain regions. In conclusion, brief ischemic episodes induce an hyperactive, anxious but not depressive phenotype in mice, that may relate to left versus right hemispheric lesion location, specific alterations in brain monoamine levels and selective neurodegeneration.