The neuroprotective influence of the glutamatergic modulator acamprosate on neurological outcome after experimental cerebral ischemia - a comparison with the lipid peroxidation-inhibitor U-101033E

Introduction. This study investigates the effects of acamprosate, a glutama tergic modulator, and the lipid peroxidation inhibitor U-101033E on neurolo gical outcome following incomplete cerebral ischemia and reperfusion in rat s. Material and methods. Twenty-seven male Sprague-Dawley rats were randomly a ssigned to one of the following treatment groups: 1 (n=9, control, no drug treatment), 2 (n=9, 2x200 mg/kg acamprosate ip), and 3 (n=9, 2x0.3 mg/kg U- 101033E iv). Background anesthesia was maintained using a combination offen tanyl and O-2/N2O (FiO(2)=0.3). Ischemia was produced by combined unilatera l common carotid artery ligation and hemorrhagic hypotension to a mean arte rial blood pressure (MAP) of 35 mm Hg for 30 minutes. Functional neurologic al deficit was evaluated for the following 3 days after cerebral ischemia. Results. At the third postischemic day, five control animals and five anima ls treated with U-101033E were dead for stroke-related reasons. Surviving a nimals presented severe neurological deficits. In contrast, acamprosate imp roved neurological outcome,with stroke-related death occurring in one anima l only and a minor neurological deficit in the surviving rats. Discussion. The present study demonstrates that acamprosate, in contrast to U-101033E, significantly reduces neurological deficits following transient hemispheric ischemia. The neuroprotective mechanisms of acamprosate may be related to its antiglutamatergic effect with consecutive reduction of tran smembraneous Ca++ flux through NMDA-activated ion channels.