EFFECT OF ACETYL-L-CARNITINE ON RECOVERY OF BRAIN PHOSPHORUS METABOLITES AND LACTIC-ACID LEVEL DURING REPERFUSION AFTER CEREBRAL-ISCHEMIA IN THE RAT - STUDY BY P-13-NMR AND H-1-NMR SPECTROSCOPY

The effects of acetyl-L-carnitine (ALCAR) treatment on brain energy state recovery and lactic acid levels following 20 min ischemia and 2, 24 and 48 h reperfusion were investigated by P-31 and H-1-NMR spectroscopy. Transient forebrain ischemia was induced by four-vessel occlusion method in fed 6-month-old Fischer rats. ALCAR or saline was administered by intraperitoneal route immediately after 20 min ischemia and again at 1, 4, 24 and 30 h during reperfusion. Twenty-min severe forebrain ischemia was associated with a marked decrease in phosphocreatine (PCr) and ATP levels and a corresponding increase in lactic acid, inorganic phosphate (P-i), AMP, creatine, glycerol 3-phosphate and alanine levels. Following reperfusion, a general tendency to restore pre-ischemic metabolite levels was observed. However, after 2 h reperfusion in saline-treated rats, lactic acid and P-i levels remained significantly higher, while ATP levels were still significantly lower than in non-ischemic controls. On the contrary, in ALCAR-treated animals a complete recovery of all metabolites including P-i and ATP was observed, while PCr levels were even more elevated compared with those in saline-treated rats. Furthermore lactic acid content was significantly lower than that in both saline-treated and non-ischemic control rats. It is concluded that a potential therapeutic role may be claimed for ALCAR in the treatment of cerebral ischemia through mechanisms that include faster recovery and improvement of brain energy production as well as a decreased lactic acid content during early post-ischemic reperfusion.