Blood flow compensates oxygen demand in the vulnerable CA3 region of the hippocampus during kainate-induced seizures

Local blood flow, and partial pressures of oxygen and carbon dioxide were directly monitored in the vulnerable region of Ammon's horn (e.g. CA3) of unanaesthetized, freely breathing rats in which epileptic seizures of 120 min duration were induced by parenteral kainic acid. Blood flow was periodically determined by helium clearance. Partial pressures of oxygen and carbon dioxide were simultaneously and continuously measured by means of mass spectrometry, in order to determine if the neuronal damage occurring during the seizures were due to local hypoxia or if blood flow compensated the metabolic demand. During the wet shakes period, a decrease of 35% in the partial pressure of oxygen occurred, concomitant with an increase of 33% in the partial pressure of carbon dioxide and of 330% in local blood flow in Ammon's horn. During the limbic motor seizures, the partial pressure of oxygen increased progressively to twice its baseline value, while the partial pressure of carbon dioxide returned to its baseline value and blood flow underwent a six-fold increase. Thus the seizures produced by kainate do not lead to a mismatch between oxygen supply and blood flow. Our results provide direct evidence that hypoxia cannot be considered responsible for the damage produced by the seizures in CA3. It is concluded that brain damage in CA3 is due to an enhanced neuronal activity associated with the release of a toxic endogenous substance and an excessive rise of intracellular concentration of calcium.