TY - JOUR PY - 2018// TI - Primary blast causes delayed effects without cell death in shell-encased brain cell aggregates JO - Journal of neurotrauma A1 - Sawyer, Thomas A1 - Wang, Yushan A1 - Ritzel, David V. A1 - Josey, Tyson A1 - Villanueva, Mercy A1 - Vair, Cory A1 - Song, Yanfeng A1 - Shei, Yimin A1 - Parks, Steven A1 - Nelson, Peggy A1 - Hennes, Grant A1 - McLaws, Lori A1 - Fan, Changyan SP - 174 EP - 186 VL - 35 IS - 1 N2 - 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

LA - en SN - 0897-7151 UR - http://dx.doi.org/10.1089/neu.2016.4961 ID - ref1 ER -