Spreading depolarizations occur in mild traumatic brain injuries and are associated with postinjury behavior

Abstract

Millions of people suffer mild traumatic brain injuries (mTBIs) every year, and there is growing evidence that repeated injuries can result in long-term pathology. The acute symptoms of these injuries may or may not include the loss of consciousness but do include disorientation, confusion, and/or the inability to concentrate. Most of these acute symptoms spontaneously resolve within a few hours or days. However, the underlying physiological and cellular mechanisms remain unclear. Spreading depolarizations (SDs) are known to occur in rodents and humans following moderate and severe TBIs, and SDs have long been hypothesized to occur in more mild injuries. Using a closed skull impact model, we investigated the presence of SDs immediately following a mTBI. Animals remained motionless for multiple minutes following an impact and once recovered had fewer episodes of movement. We recorded the defining electrophysiological properties of SDs, including the large extracellular field potential shifts and suppression of high-frequency cortical activity. Impact-induced SDs were also associated with a propagating wave of reduced cerebral blood flow (CBF). In the wake of the SD, there was a prolonged period of reduced CBF that recovered in approximately 90 min. Similar to SDs in more severe injuries, the impact-induced SDs could be blocked with ketamine. Interestingly, impacts at a slower velocity did not produce the prolonged immobility and did not initiate SDs. Our data suggest that SDs play a significant role in mTBIs and SDs may contribute to the acute symptoms of mTBIs.