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 31P and 1H-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 (
Pi), 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 Pi 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 Pi 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.