Techniques for termination of reverberating spreading depression in rats

Abstract

Reverberation of cortical spreading depression (CSD) around a circular obstacle (thermocoagulation lesion) in the frontal cortex of anesthetized rats was elicited by appropriately timed and spaced applications of KCl. The probability of continued reverberation was increased by a pyrrolopyrimidine drug BW 58-271 (10 mg/kg) from 0.93 to 0.98. Three methods of reverberation arrest were tested: a) CSD propagation was blocked by an interfering CSD wave which was initiated in the rear of the reverberating wave, passing through a narrow segment of the circular pathway, and collided with the reverberating wave on the opposite side of the obstacle; b) CSD propagation through a part of the circular pathway was blocked by a 10-min application of 10% MgCl2 on the exposed cortical surface; c) 1-min asphyxia stopped RCSD by increasing the overall refractoriness of cortical tissue. Least reliable was the interference method which stopped reverberation, even with optimum timing, only in 42% of the trials. The magnesium blockade was reliable but slow, the reverberation stopping only 30 min after MgCl2 application. Asphyxia evoked in any phase of the reverberation cycle stopped RCSD reliably and immediately. The results obtained with the interference method confirm the predictions of the mathematical model of impulse reverberation in sheets of excitable tissue. Anoxia seems best suited for practical control of CSD reverberation in functional decortication studies.