[Effects of S-adenosyl-L-methionine on the cerebral energy metabolism and microcirculation in the rats subjected to transient forebrain ischemia].

Effects of S-adenosyl-L-methionine (SAM) on the improvement of cerebral energy metabolism and microcirculation were examined in postischemic rat brain. Male Wistar rats, whose vertebral arteries were electrically cauterized last day, were subjected to forebrain ischemia by temporary clipping of both common carotid arteries. After 60 min of ischemic insult, they were intravenously administered with SAM at doses of 30 or 100 mg/kg; this was followed by recirculation for 60 min. To determine cerebral concentrations of energy metabolites, the brain was frozen in situ. Adenine nucleotides (ATP, ADP, AMP) were assayed by anion-exchange HPLC system, and other metabolites (PCr, glucose, lactate, pyruvate) were analyzed by enzymatic fluorometry. In order to estimate regional cerebral blood flow (rCBF) and glucose utilization, double-tracer autoradiography was undertaken using 14C-iodoantipyrine (14C-IAP) and 18F-fluorodeoxyglucose (18F-FDG). In animals without SAM treatment (60-60 group), energy metabolites did not recover and neither CBF nor glucose uptake restored during 60 min of recirculation. In contrast, in SAM-treated animals (60-60 SAM group), values of the energy metabolites improved significantly and both CBF and glucose uptake recovered, though incompletely. These results indicate that SAM is able to improve postischemic cerebral microcirculation and energy metabolism. For mechanisms of the effects, it is suggested to the enhancement of erythrocyte deformability by phospholipid methylation, the stabilization of mitochondria, and the normalization of injured metabolic reactions. Therefore, we conclude that SAM is able to be effective clinically as a drug treated for the acute phase of cerebrovascular diseases.