Citation

Silvosa MJ, Romo Mercado N, Merlock N, Vidhate S, Mejia-Alvarez R, Yuan T, Willis AM, Lybrand ZR. J. Neurotrauma 2022; ePub(ePub): ePub.

Copyright

(Copyright © 2022, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2022.0044

PMID

35765922

Abstract

Blast exposure represents a common occupational risk capable of generating mild to severe traumatic brain injuries (TBI). During blast exposure, a pressure shockwave passes through the skull and exposes brain tissue to complex pressure waveforms. The primary neurophysiological response to blast-induced pressure waveforms remains poorly understood. Here, we use a computer-controlled table-top pressure chamber to expose human stem cell-derived cerebral organoids to varied frequency of pressure waves and characterize the neurophysiological response. Pressure waves that reach a maximum amplitude of 250kPa were used to model a less severe TBI and 350kPa for a more severe blast TBI event. With each amplitude, a frequency range of 500Hz, 3000Hz, and 5000Hz was tested. Following the 250 kPa overpressure a multielectrode array recorded organoid neural activity. We observed an acute suppression neuronal activity in single unit events, population events, and network oscillations that recovered within 24 hours. Additionally, we observed a network desynchronization after exposure higher frequency waveforms. Conversely, organoids exposed to higher amplitude pressure (350kPa) displayed drastic neurophysiological differences that failed to recover within 24 hours. Furthermore, lower amplitude 'blast' (250kPa) did not induce cellular damage whereas the higher amplitude 'blast' (350kPa) generated greater apoptosis throughout each organoid. Our data indicate that specific features of pressure waves found intracranially during blast TBI have varied effects on neurophysiological activity that can occur even without cellular damage.

Language: en

Keywords

TRAUMATIC BRAIN INJURY; NEURONAL CELL DEATH; STEM CELLS