Repetitive cortical spreading depolarizations are prolonged early after experimental traumatic brain injury

Abstract

Cortical spreading depolarizations (CSDs) are the most common electrophysiological dysfunction following a traumatic brain injury (TBI), and clustered CSDs (≥3 CSDs in 2 h) are associated with poor outcomes 6 months after TBI. While many experimental studies have investigated a single CSD after injury, no known studies have investigated how time after injury affects the characteristics and impact of a CSD cluster. This study sought to determine the characteristics of a cluster of repetitive CSDs when induced at three different time points after moderate experimental TBI. Adult male Sprague Dawley rats underwent a lateral fluid percussion or sham injury, and repetitive CSDs were induced 0-, 3-, or 7-days post injury (dpi). Properties were analyzed from 2-h-long electrocorticographic (ECoG) and laser Doppler flowmetry (LDF) recordings. We did not observe deterioration of CSDs (2-Way ANOVA, p = 0.3572), depressions of background electrical activity (p = 0.0991), or hemodynamic responses (p = 0.1298) over the course of the recording. Repetitive CSD direct current shift durations were the longest when induced at 0dpi (p = 0.0161), while the durations of CSDs induced at 3dpi and 7dpi were similar to CSD durations in uninjured tissue (p = 0.9857). No differences were seen in the depression of background activity duration (p = 0.1901), and normal hemodynamic responses were observed at each time point. These findings confirm that CSDs are prolonged in impaired tissue and suggest that the impaired tissue may be more at risk of further damage when repetitive CSDs occur early after injury.