Ischemic brain slice glucose utilization: effects of slice thickness, acidosis, and K+.
Brain slices of varying thickness were used to modify retention of metabolic products in an in vitro model of ischemia. Past and present results reveal increased anaerobic glycolysis in 660-microns slices with accumulation of lactate as slice thickness reaches 1,000 microns. Brain slice glucose utilization and lactate content were measured in buffers of various extracellular K+ levels and pH in 540-, 660-, and 1,000-microns slices. Acidosis suppresses glucose utilization at all slice thicknesses without affecting tissue lactate. Studies of 2-deoxyglucose metabolites establish that the suppression of glucose utilization by acidosis is due entirely to inhibition of glucose phosphorylation without any effect on glucose uptake into tissue. The inhibition is reversible after 45 min at pH 6.1. The experiments with acidosis also suggest that persistent energy demands continue to stimulate phosphofructokinase despite the low pH so that glycolysis continues, with potential for injury. Increasing K+ increases glucose utilization and tissue lactate at all three thicknesses. Correlations of glucose utilization with lactate accumulation support the possibility that high K+ may exert a dual influence on the tissue metabolism, not only stimulating glucose utilization by inducing depolarization but also by influencing the removal of metabolic products.
Newman
G C
GC
Neurology Service, Veterans Administration Medical Center, Northport, New York.
Hospod
F E
FE
Schissel
S L
SL
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002021:Buffers; D003847:Deoxyglucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006863:Hydrogen-Ion Concentration; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D010766:Phosphorylation; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002021:Buffers; D007773:Lactates; D019344:Lactic Acid; D003847:Deoxyglucose; D005947:Glucose; D011188:Potassium