Protective effect of clonazepam on ischemic brain damage induced by 10-minute bilateral carotid occlusion in...

A 10-min bilateral carotid occlusion (BCO) in a control group of Mongolian gerbils, induced a transient generalized epileptic activity both in the hippocampal and in the cortical regions, associated with motor manifestations. After recirculation, spiking activity persisted, reaching its maximum peak within 18-36 h and then slowly decreasing till its total disappearance on the 6th-7th day. On the 7th day, histological studies manifested a selective loss of CA1 hippocampal neurons. The treated gerbils (divided in 2 groups according to the dosage used) were administered clonazepam (CZP), a benzodiazepine receptor agonist, immediately after clamping and again every 24 h for the following three days at dosages of 0.05 and 0.1 mg/kg i.p., respectively. The drug inhibited epileptic activity in a dose-dependent manner, while it prevented CA1 neuronal loss at both doses. These results point to a possible derangement of the GABAergic system which probably in turn triggers an exaggerated excitation.