Altered gene expression in cultured microglia in response to simulated blast overpressure: possible role of pulse duration.
Blast overpressure has long been known to cause barotrauma to air-filled organs such as lung and middle ear. However, experience in Iraq and Afghanistan is revealing that individuals exposed to explosive munitions can also suffer traumatic brain injury (TBI) even in the absence of obvious external injury. The interaction of a blast shock wave with the brain in the intact cranial vault is extremely complex making it difficult to conclude that a blast wave interacts in a direct manner with the brain to cause injury. In an attempt to "isolate" the shock wave and test its primary effects on cells, we exposed cultured microglia to simulated blast overpressure in a barochamber. Overpressures ranging from 15 to 45 psi did not change microglial Cox-2 levels or TNF-α secretion nor did they cause cell damage. Microarray analysis revealed increases in expression of a number of microglial genes relating to immune function and inflammatory responses to include Saa3, Irg1, Fas and CxCl10. All changes in gene expression were dependent on pulse duration and were independent of pressure. These results indicate that microglia are mildly activated by blast overpressure and uncover a heretofore undocumented role for pulse duration in this process.
Research & Development Service, John D. Dingell VA Medical Center, Detroit, MI 48201, USA.
Michael J
MJ
Kane
Mariana
M
Angoa-Pérez
Dina M
DM
Francescutti
Catherine E
CE
Sykes
Denise I
DI
Briggs
Lai Yee
LY
Leung
Pamela J
PJ
VandeVord
Donald M
DM
Kuhn
D000818:Animals; D001753:Blast Injuries / Q000378:metabolism*; D002460:Cell Line; D020869:Gene Expression Profiling; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011312:Pressure; D013997:Time Factors