[The neuroprotective effect of the glutamate antagonist acamprosate following experimental cerebral ischemia. A study with the lipid peroxidase inhibitor u-101033e].
BACKGROUND
This 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.


METHODS
Twenty-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.


RESULTS
At 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.


CONCLUSIONS
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 transmembraneous Ca++ flux through NMDA-activated ion channels.
Engelhard
K
K
Klinik für Anaesthesiologie der, Klinikum rechts der Isar, Technischen Universität München.
Werner
C
C
Lu
H
H
Möllenberg
O
O
Zieglgänsberger
W
W
Kochs
E
E
D000077443:Acamprosate; D000427:Alcohol Deterrents / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000633:toxicity; D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005283:Fentanyl / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009195:Peroxidase / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000427:Alcohol Deterrents; D018686:Anesthetics, Intravenous; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D011743:Pyrimidines; D011759:Pyrrolidines; C101923:U 101033E; D013654:Taurine; D009195:Peroxidase; D000077443:Acamprosate; D005283:Fentanyl