• K Engelhard, C Werner, H Lu, O Möllenberg, W Zieglgänsberger, and E Kochs.
• Klinik für Anaesthesiologie der, Klinikum rechts der Isar, Technischen Universität München.
• Anaesthesist. 2000 Sep 1; 49 (9): 816-21.

IntroductionThis study investigates the effects of acamprosate, a glutamatergic modulator, and the lipid peroxidation inhibitor U-101033E on neurological outcome following incomplete cerebral ischemia and reperfusion in rats.Material And MethodsTwenty-seven male Sprague-Dawley rats were randomly assigned to one of the following treatment groups: 1 (n = 9, control, no drug treatment), 2 (n = 9, 2 x 200 mg/kg acamprosate i.p.), and 3 (n = 9, 2 x 0.3 mg/kg U-101033E i.v.). Background anesthesia was maintained using a combination of fentanyl and O2/N2O (FiO2 = 0.3). Ischemia was produced by combined unilateral common carotid artery ligation and hemorrhagic hypotension to a mean arterial blood pressure (MAP) of 35 mm Hg for 30 minutes. Functional neurological deficit was evaluated for the following 3 days after cerebral ischemia.ResultsAt the third postischemic day, five control animals and five animals treated with U-101033E were dead for stroke-related reasons. Surviving animals presented severe neurological deficits. In contrast, acamprosate improved neurological outcome, with stroke-related death occurring in one animal only and a minor neurological deficit in the surviving rats.DiscussionThe 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 transmembraneous Ca++ flux through NMDA-activated ion channels.

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