Glycolysis and epilepsy-induced changes in cerebrocortical NAD/NADH redox state.

The effects of topical inhibition of glycolysis on epilepsy-induced changes of cortical vascular volume (CVV) and fluorescence of reduced nicotinamide adenine dinucleotide (NADH) were investigated in chloralose-anaesthetized cats. CVV and NADH fluorescence were measured by a microscope fluororeflectometer. It was found that 30 min of superfusion of the brain cortex with artificial cerebrospinal fluid (CSF) containing 0.5 mM sodium iodoacetate (IAA) resulted in a 16.4 +/- 0.8% increase in CVV, and 6.6 +/- 0.5% in NADH oxidation. IAA did not alter the electrical activity of the brain cortex. Epileptic seizures in the nonsuperfused brain cortex and following 30 min superfusion of the brain cortex with mock CSF resulted in changes (not significantly different) in CVV and NAD/NADH redox state. They increased CVV and NAD reduction by 28-32% and 7-10%, respectively. Following 0.5 mM IAA treatment of the brain cortex, epileptic seizures led to greatly reduced vascular responses and induced NADH oxidation instead of NAD reduction. Since the topical inhibition of glycolysis reversed the direction of NAD/NADH redox responses accompanying epilepsy, it may be suggested that the relative rate of substrate mobilization as compared with the rate of mitochondrial electron transport is the factor that determines the actual change in NAD-NADH ratio during excessive brain activations. However, contrary to the situation in vitro (isolated mitochondria), the NAD/NADH redox state of the intact brain cortex is not shifted toward oxidation but to reduction during increased electrical activity.