Citation

Sawyer T, Wang Y, Ritzel DV, Josey T, Villanueva M, Vair C, Song Y, Shei Y, Parks S, Nelson P, Hennes G, McLaws L, Fan C. J. Neurotrauma 2018; 35(1): 174-186.

Affiliation

DRDC Suffield Research Centre, Medicine Hat, Alberta, Canada ; Changyang.fan@drdc-rddc.gc.ca.

Copyright

(Copyright © 2018, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2016.4961

PMID

28726571

Abstract

Previous work used underwater explosive exposures to isolate the effects of shock-induced principle stress without shear on rat brain aggregate cultures. This current study has utilized simulated air blast to expose aggregates in suspension and enclosed within a spherical shell, enabling the examination of a much more complex biomechanical insult. Culture medium-filled spheres were exposed to single pulse overpressures of 15-30 psi (6-7 msec duration) and measurements within the sphere at defined sites showed complex and spatially dependent pressure changes. When brain aggregates were exposed to similar conditions, no cell death was observed, and no changes in several commonly used biomarkers of traumatic brain injury (TBI) were noted. However, similarly to underwater blast, immediate and transient increases in the Akt signaling pathway were observed at early time points (three days). In contrast, the oligodendrocyte marker 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), as well as vascular endothelial growth factor (VEGF) both displayed markedly delayed (14-28 days) and pressure-dependent responses. The imposition of a spherical shell between the single pulse shock wave and the target brain tissue introduces greatly increased complexity to the insult. This work shows that brain tissue can not only discriminate the nature of the pressure changes it experiences, but that a portion of its response is significantly delayed. These results have mechanistic implications for the study of primary blast-induced TBI and also highlight the importance of rigorously characterizing the actual pressure variations experienced by target tissue in primary blast studies.

Language: en

Keywords

BIOMARKERS; IN VITRO STUDIES; MODELS OF INJURY; TRAUMATIC BRAIN INJURY