Lactate accumulation following concussive brain injury: the role of ionic fluxes induced by excitatory amino acids.
During the first few minutes following traumatic brain injury, cells are exposed to an indiscriminate release of glutamate from nerve terminals resulting in a massive ionic flux (e.g., K+ efflux) via stimulation of excitatory amino acid (EAA)-coupled ion channels. The present study was undertaken to elucidate the causal relationship between these ionic shifts and lactate accumulation in the injured brain, by examining the effects of ouabain (an inhibitor of Na+/K+-ATPase), Ba2+ (an inhibitor or non-energy-dependent glial K+ uptake) and kynurenic acid (KYN; a broad-spectrum EAA antagonist) on lactate accumulation. Two microdialysis probes were placed bilaterally in the rat parietal cortex. One was perfused with a test drug (1.0 mM ouabain, 2.0 mM Ba2+ or 10 mM KYN) and the other with Ringer's solution (control) for 30 min prior to injury. Following a 2.2-2.7 atm fluid-percussion injury, lactate levels in the dialysate increased (up to 116.6% above baseline) for the first 16 min and returned to baseline levels within 20 min after injury. This lactate accumulation was attenuated by preinjury administration of ouabain and KYN and was prolonged by Ba2+ administration. These findings indicate that lactate accumulations following concussive brain injury is a result of increased glycolysis which supports ion-pumping mechanisms, thereby, restoring the ionic balance which was disrupted by stimulation of EAA-coupled ion channels.
Kawamata
T
T
Division of Neurosurgery, ULCA School of Medicine 90024-6901, USA.
Katayama
Y
Y
Hovda
D A
DA
Yoshino
A
A
Becker
D P
DP
D000818:Animals; D001464:Barium / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001924:Brain Concussion / Q000097:blood / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D018846:Excitatory Amino Acids / Q000502:physiology*; D005110:Extracellular Space / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D007736:Kynurenic Acid / Q000494:pharmacology; D007773:Lactates / Q000097:blood / Q000378:metabolism*; D019344:Lactic Acid; D008297:Male; D017551:Microdialysis; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D018846:Excitatory Amino Acids; D007473:Ion Channels; D007773:Lactates; D001464:Barium; D019344:Lactic Acid; D010042:Ouabain; D007736:Kynurenic Acid