Dynamic changes in cerebral oxygenation in chemically induced seizures in rats: study by near-infrared spectrophotometry

Abstract

Using near-infrared spectrophotometry, the redox state of copper in cytochrome oxidase, and the hemoglobin oxygenation state were measured in the rat brain in situ during and after chemically induced seizures. Pentylentetrazol (PTZ) administration caused the partial reduction of cytochrome oxidase in the brain just before the elctroencephalogram (EEG) showed desynchronization, and then blood pressure was elevated concomitantly with an increase in cerebral blood volume. When blood pressure reached a maximum, bursts of spikes appeared on the EEG and cytochrome oxidase was reoxidized to reach the initial oxidation level, giving a rapid, transient reduction of cytochrome oxidase in the preictal period. Hemoglobin was more oxygenated than before the administration throughout the seizure. In the late postictal phase, cytochrome oxidase was partially reduced again, while blood pressure remained high and hemoglobin was more oxygenated than initially. The second administration of PTZ in the late postictal phase induced the same responses as observed after the first administration. By decreasing oxygen concentrations in the inspired gas during the seizure, cytochrome oxidase was more reduced than in the non-epileptic rat, and spike activity was observed until about 85% of cytochrome oxidase was reduced. The transient cerebral hypoxia reflected by the reduction of cytochrome oxidase in the preictal period may be a trigger for an increase in cerebral blood flow rather than the result of a delayed autonomic response. The second reduction of cytochrome oxidase observed in the late postictal phase may be due to a lasting arterio-venous shunt that opens during seizures. These results revive the classical theory that cellular hypoxia is responsible for epileptic brain damage.