Behavioral recovery from unilateral photothrombotic infarcts of the forelimb sensorimotor cortex in rats: role of the contralateral cortex.

During sensorimotor recovery following stroke ipsi- and contralesional alterations in brain function have been characterized in patients as well as animal models of focal ischemia, but the contribution of these bilateral processes to the functional improvement is only poorly understood. Here we examined the role of the homotopic contralateral cortex for sensorimotor recovery after focal ischemic infarcts at different time periods after the insult. One group of animals received a unilateral single photothrombotic infarct in the forelimb sensorimotor cortex, while four additional groups received a second lesion in the contralateral homotopic cortex either immediately or 2 days, 7 days, or 10 days after the first infarct. The time course of functional recovery of the impaired forelimbs was assessed using different sensorimotor scores: forelimb-activity during exploratory behavior and frequency of forelimb-sliding in the glass cylinder as well as forelimb misplacement during grid walking. Focal infarcts in the forelimb sensorimotor cortex area significantly impaired the function of the contralateral forelimb in these different behavioral tests. The subsequent damage of the contralateral homotopic forelimb sensorimotor cortex only affected the forelimb opposite to the new lesion but did not reinstate the original deficit. The time course of sensorimotor recovery after bilateral sequential cortical infarcts did not significantly differ from animals with unilateral single lesions. These data indicate that following small ischemic cortical infarcts in the forelimb sensorimotor cortex the contralateral cortex homotopic to the lesion plays only a minor role for functional recovery.

Memory restoring and neuroprotective effects of the proline-containing dipeptide, GVS-111, in a photochemical stroke model.

Local thrombosis of the frontal cortex (Fr1 and Fr3 fields), caused by combination of the intravenous photosensitive dye Rose Bengal administration with focused high-intensity illumination of the frontal bone, was shown to provoke a pronounced deficit in step-through passive avoidance performance in rats without concomitant motor disturbances. N-Phenylacetyl-L-prolylglycine ethyl ester (GVS-111) administered intravenously at a dose of 0.5 mg/kg/day, for the first time 1 h after ischaemic lesion and then for 9 post-operative days, with the last administration 15 min before testing, attenuated the deficit. This treatment significantly diminished the volume of the infarcted area. Thus, post-ischaemic injection of GVS-111 demonstrated both cognition-restoring and neuroprotective properties. The cognition-restoring effect is probably based on an increase in neocortical and hippocampal neuronal plasticity. Neuroprotective effects of GVS-111 combine antioxidant activity with the ability to attenuate glutamate-provoked neurotoxicity and block voltage-gated ionic channels, i.e. the compound mitigates the main metabolic shifts involved in pathogenesis of brain ischaemia.