The Coupling between Epilepsy and Cortical Spreading Depression of Leão

Abstract

Objectives: The discovery of cortical spreading depression 80 years ago by Leão was intimately connected to epilepsy research. In our studies we found that monitoring of brain hemodynamics, metabolic ionic and electrical activities are very similar in the two pathophysiological events. Here we are presenting the coupling between epilepsy and cortical spreading depression while monitoring of mitochondrial nicotinamide adenine dinucleotide-NADH together with other physiological parameters in real time in vivo. Methods: Rats and Mongolian gerbils were used in three models of induction of epilepsy, namely injection of pentylenetetrazol-metrazol, exposure of the rats to hyperbaric oxygenation in a pressure chamber and using a strain of gerbils that are developing seizures spontaneously. We monitored brain oxygen levels, mitochondrial NADH, extracellular potassium levels, Direct Current-DC steady potential and electroencephalography-EEG in the very slightly anesthetized animals. Results: The results could be summarized as follows: 1. In almost all animal tested cortical spreading depression was developed and recorded after 1-3 minutes of seizures activity. 2. Mitochondrial NADH redox state was more oxidized during the two events. 3. The oxidation of NADH during the Cortical Spreading Depression- CSD was 3-4 times relative to the seizure’s interval. 4. The increase in extracellular potassium levels was also 3-4 times higher during the CSD event. Significance: Under the two recorded events a clear correlation between the process of oxygen (energy) demand or consumption and oxygen (energy) supply was found. The results suggest that the accumulation of extracellular potassium during the epileptic activity is probably the trigger for the development of CSD in the 3 model used.