Citation

Pacheco J, Hines-Lanham A, Stratton C, Mehos CJ, McCurdy KE, Pinkowski NJ, Zhang H, Shuttleworth CW, Morton RA. eNeuro 2019; ePub(ePub): ePub.

Affiliation

Department of Neurosciences University of New Mexico School of Medicine. Albuquerque, NM, United States. ramorton@salud.unm.edu.

Copyright

(Copyright © 2019, Society for Neuroscience)

DOI

10.1523/ENEURO.0070-19.2019

PMID

31748237

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. In the wake of the SD, there was a prolonged period of reduced CBF that recovered in approximately 90 minutes. 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.Significance Statement Millions of people suffer from concussions every year and repeated concussions are associated with Chronic Traumatic Encephalopathy (CTE). Spreading Depolarizations (SDs) are propagating waves of brain tissue depolarization that have been associated with strokes, subarachnoid hemorrhages, and moderate to severe brain injuries. SDs have long been hypothesized to occur in mild brain injuries, but have not been recorded. Our studies are the first to directly record the electrophysiological properties of SDs following a closed skull impact, and suggest that SDs may contribute to the acute symptoms of mTBIs.

Copyright © 2019 Pacheco et al.

Language: en

Keywords

Cerebral blood flow; Concussion; Cortical spreading depression; Laser speckle contrast imaging; closed skull impact; electrophysiology