Protective effect of dichloroacetate in a rat model of forebrain ischemia.
Dichloroacetate (DCA) activates the pyruvate dehydrogenase complex (PDHC), and improves the recovery of cerebral pH, lactate, ATP, and PCr following reperfusion in animal models of forebrain ischemia. In order to determine whether this results in neuroprotection, rats were administered NaDCA (100 mg/kg or 10mg/kg i.v.) 10 min before 12 min of normothermic forebrain ischemia (bilateral carotid artery occlusion plus systemic hypotension, 45 mmHg). Neuronal injury assessed histopathologically 7 days post-ischemia was significantly reduced in the CA1 region of the hippocampus, the dorsal lateral striatum, and the neocortex, in rats treated with 100 mg/kg NaDCA, but not in rats treated with 10 mg/kg NaDCA.
Peeling
J
J
Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada. jim@bionmr.mrrl.umanitoba.ca
Sutherland
G
G
Brown
R A
RA
Curry
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003999:Dichloroacetic Acid / Q000627:therapeutic use*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008297:Male; D017072:Neostriatum / Q000378:metabolism / Q000473:pathology; D010725:Phosphocreatine / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism / Q000473:pathology*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D011768:Pyruvate Dehydrogenase Complex; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003999:Dichloroacetic Acid