Metabolic changes associated with altering blood glucose levels in short duration forebrain ischemia.
31P nuclear magnetic resonance spectroscopy was used to follow changes in cerebral pH and high-energy phosphate metabolites during forebrain ischemia in hypo-, normo- and hyperglycemic rats, and during reperfusion in animals in which the blood glucose level was altered post-ischemia. Pre-ischemia, no differences in the levels of inorganic phosphate (Pi) and adenosine triphosphate (ATP) relative to phosphocreatine (PCr) or in tissue pH between blood glucose groups were observed. During ischemia, the decrease in tissue pH was found to be dependent on the pre-ischemic blood glucose concentration, being greatest in hyperglycemic and least in hypoglycemic animals. The increase of Pi, a consequence of the hydrolysis of high-energy phosphate metabolites, also depended on the blood glucose concentration, being greatest in hypoglycemic and least in hyperglycemic animals. ATP and PCr decreased more rapidly in hypoglycemic rats compared to normo- or hyperglycemic animals, which showed no differences in the rates of depletion. Post-ischemic hyperglycemia resulted in delayed recovery of tissue pH in all groups and of PCr and ATP in animals hyperglycemic throughout the experiment. Insulin administration immediately following ischemia increased the rate of recovery of pH, ATP and PCr in hyperglycemic animals. ATP remained significantly below pre-ischemia level in all subgroups at 1 h post-ischemic, while PCr was lower than it was pre-ischemia only in those subgroups hyperglycemic prior to and/or following ischemia. In animals maintained severely hypoglycemic throughout the experiment, erratic blood pressure and cerebral energy failure during the reperfusion interval were observed.
Department of Chemistry, University of Manitoba, Winnipeg, Canada.
R
R
Tyson
J
J
Peeling
G
G
Sutherland
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D016548:Prosencephalon / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism
D001786:Blood Glucose; D010710:Phosphates; D010725:Phosphocreatine; C012058:tenocyclidine; D000255:Adenosine Triphosphate; D010622:Phencyclidine