Seizure activity and cortical spreading depression monitored by an extrinsic potential-sensitive molecular probe

Using surface fluorescence and reflectance measurements from the exposed cerebral cortex, several potential-sensitive molecular probes, primarily oxonol V, have been evaluated as indicators of electrical activity changes developing during seizure activity in the mongolian gerbil. Intraventricular injection of bicuculline, picrotoxin, or KCl produced characteristic cyclic molecular probe fluorescence intensity decreases that could be abolished by the uncoupler CCCP or the mitochondrial electron transport inhibitor rotenone. Smaller fluorophore signals were observed when KCl was applied topically to the exposed cortex. In some cases, as the animals were recovering from anoxia induced by nitrogen inhalation, oscillations similar to those due to spreading depression were observed in both the oxonol V and pyridine nucleotide signals. In all experiments, the molecular probe signals closely followed those of the intrinsic pyridine nucleotides. The drug-induced oxonol V signal alterations have been provisionally interpreted as due at least in part to the reduction of the mitochondrial membrane potential that accompanies a state 4 to state 3 transition. Measurements at the oxonol V fluorescence excitation wavelength indicated that only small changes in the reflectance signal occurred during seizure activity suggesting minimal blood volume change contributions to the extrinsic probe signal.