Primary Blast Causes Delayed Effects without Cell Death in Shell-Encased Brain Cell Aggregates

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Authors
  1. Sawyer, T.W.
  2. Ritzel, D.V.
  3. Wang, Y.
  4. Josey, T.
  5. Villanueva, M.
  6. Nelson, P.
  7. Song, Y.
  8. Shei, Y.
  9. Hennes, G.
  10. Vair, C.
  11. Parks, S.
  12. Fan, C.
Corporate Authors
Defence Research and Development Canada, Suffield Research Centre, Ralston AB (CAN);Dyn-FX Consulting Limited, Amherstburg ON (CAN);ORA Inc, Marion, North Carolina (US);Canada West Biosciences Inc, Camrose Alta (CAN)
Abstract
Previous work in this laboratory used underwater explosive exposures to isolate the effects of shock-induced principle stress without shear on rat brain aggregate cultures. The 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 protein kinase B signaling pathway were observed at early time–points (3 days). In contrast, the oligodendrocyte marker 2’,3’-cyclic nucleotide 3’-phosphodiesterase, as well as vascular endothelial growth factor, 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 m
Keywords
Akt (protein kinase B;Advanced Blast Simulator (ABS);Blast-induced brain injury;Primary Blast;Traumatic Brain Injury (TBI);Vascular Endothelial Growth Factor (VEGF)
Report Number
DRDC-RDDC-2017-P090 — External Literature
Date of publication
01 Oct 2017
Number of Pages
18
DSTKIM No
CA045428
CANDIS No
805836
Format(s):
Electronic Document(PDF)

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