Fasting prior to transient cerebral ischemia reduces delayed neuronal necrosis.
A transient brain ischemia of 30-min duration was induced by the four-vessel occlusion technique in normally fed and in 48-hr-fasted rats. Evaluation of brain damage 72 hr after ischemia showed that fasting reduced neuronal necrosis in the striatum, the neocortex, and the lateral part of the CA1 sector of hippocampus. Signs of status spongiosis in the pars reticulata of the substantia nigra were seen in 75% of fed rats and in only 19% of fasted rats. The protective effect was associated with reduction in mortality and in postischemic seizure incidence. The metabolic changes induced by fasting were evaluated before and during ischemia. After 30 min of four-vessel occlusion, fasted rats showed a marked decrease in brain lactate level (14.7 vs 22.5 mumol/g in fed rats; P less than 0.001). The decrease in brain lactate concentration might explain the beneficial effect of fasting by minimizing the neuropathological consequences of lactic acidosis. Several factors may account for lower lactate production during ischemia in fasted rats: hypoglycemia, reduction in preischemic stores of glucose and glycogen, or increased utilization of ketone bodies aiming at reducing the glycolytic rate.
Marie
C
C
Laboratoire de Pharmacodynamie et Physiologie Pharmaceutique, Faculté de Pharmacie, Université de Bourgogne, Dijon, France.
Bralet
A M
AM
Gueldry
S
S
Bralet
J
J
D020155:3-Hydroxybutyric Acid; D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004734:Energy Metabolism; D005215:Fasting; D005947:Glucose / Q000378:metabolism; D006885:Hydroxybutyrates / Q000097:blood; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007773:Lactates / Q000378:metabolism; D008297:Male; D009336:Necrosis; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D000227:Adenine Nucleotides; D001786:Blood Glucose; D006885:Hydroxybutyrates; D007773:Lactates; D005947:Glucose; D020155:3-Hydroxybutyric Acid