Functional and metabolic correlates of long series of cortical spreading depression waves in rats

Repetitive generation of spreading depression (SD) waves may induce metabolic and functional disturbances in the invaded brain regions. In order to better characterize this state, up to 60 SD waves were elicited in the cerebral cortex of anesthetized rats by intracortical injections of 2 microliters of isotonic K-acetate repeated at regular 5-min intervals. Propagation rate of SD between capillary electrodes located 1 mm and 7 mm from the injection site gradually decreased and after 35-45 waves became irregular. In another series of experiments SD-induced changes of cyclic adenosine monophosphate (cAMP) level were examined after 24 SD waves. Although no irregularities of SD propagation were observed, maximum level of cAMP in the SD-invaded cortex decreased from 270% in controls to 170% after 24 waves. Also, the recovery of the nucleotide was slowed down. Metabolic alterations thus preceded irregularities in SD propagation.