Ischemia-induced alterations in oxidative "recovery" metabolism after spreading cortical depression in situ.

Surface electrical stimulation was used to provoke direct cortical responses, spreading cortical depression, and concomitant increases in oxidative metabolic activity in cat neocortex in situ during and after short periods of incomplete and complete ischemia. These metabolic changes were recorded continuously in the intact tissue by monitoring the fluorescence of NADH (as NAD⁺ does not fluoresce under these optical conditions). Ischemic effects were unidirectional and progressive with the degree of perfusion decrease. Incomplete ischemia was accompanied by decreased excitability and amplitude of metabolic responses to stimulation. During incomplete ischemia when the NADH:NAD⁺ ratio was increased, the brain continued to respond to spreading cortical depression with oxidation of NADH indicating that the capability for increased respiration still resided within the tissue. In cats that survived complete ischemia, these reaction rates became unchanged from control. In other cats, the rate of NAD⁺ re-reduction after spreading depression continued to decrease and death inevitably followed. These findings confirm that short ischemic periods produce alterations in oxidative metabolic capabilities indicative of respiratory uncoupling, resulting in decreased excitability and decreased capacity to respond to increased metabolic demand.