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 st ate recovery and lactic acid levels following 20 min ischemia and 2, 2 4 and 48 h reperfusion were investigated by P-31 and H-1-NMR spectrosc opy. Transient forebrain ischemia was induced by four-vessel occlusion method in fed 6-month-old Fischer rats. ALCAR or saline was administe red by intraperitoneal route immediately after 20 min ischemia and aga in at 1, 4, 24 and 30 h during reperfusion. Twenty-min severe forebrai n ischemia was associated with a marked decrease in phosphocreatine (P Cr) and ATP levels and a corresponding increase in lactic acid, inorga nic phosphate (P-i), AMP, creatine, glycerol 3-phosphate and alanine l evels. Following reperfusion, a general tendency to restore pre-ischem ic metabolite levels was observed. However, after 2 h reperfusion in s aline-treated rats, lactic acid and P-i levels remained significantly higher, while ATP levels were still significantly lower than in non-is chemic 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-treat ed rats. Furthermore lactic acid content was significantly lower than that in both saline-treated and non-ischemic control rats. It is concl uded 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 decr eased lactic acid content during early post-ischemic reperfusion.