TY  - JOUR
PY  - 2014//
TI  - Repeated blast exposures cause DNA fragmentation in mice
JO  - Journal of neurotrauma
A1  - Wang, Ying
A1  - Arun, Peethambaran
A1  - Wei, Yanling
A1  - Oguntayo, Samue
A1  - Gharavi, Robert B.
A1  - Valiyaveettil, Manojkumar
A1  - Nambiar, Madhusoodana P.
A1  - Long, Joseph B.
SP  - 498
EP  - 504
VL  - 31
IS  - 5
N2  - The pathophysiology of blast-induced traumatic brain injury (TBI) and subsequent behavioral deficits are not well understood. Unraveling the mechanisms of injury is critical to derive effective countermeasures against this form of neurotrauma. Preservation of the integrity of cellular DNA is crucial for the function and survival of cells. We evaluated the effect of repeated blast exposures on the integrity of brain DNA and tested the utility of cell-free DNA (CFD) in plasma as a biomarker for the diagnosis and prognosis of blast-induced polytrauma. The results revealed time-dependent breakdown in cellular DNA in different brain regions, with the maximum damage at 24 h post-blast exposure. CFD levels in the plasma showed a significant transient increase which was largely independent of the timing and severity of brain DNA damage; maximum levels were recorded at 2 h after repeated blast exposure and returned to baseline at 24 h. A positive correlation was observed between CFD level in the plasma and righting reflex time at 2 h after blast exposure. Brain DNA damage following repeated blast was associated with decreased mitochondrial membrane potential, increased release of cytochrome C, and up-regulation of caspase-3, all of which are indicative of cellular apoptosis. Shockwave-induced DNA damage and initiation of mitochondrial-driven cellular apoptosis in the brain after repeated blast exposure indicate that therapeutic strategies directed towards inhibition of DNA damage or instigation of DNA repair may be effective countermeasures.<p />  <p>Language: en</p>
LA  - en
SN  - 0897-7151
UR  - http://dx.doi.org/10.1089/neu.2013.3074
ID  - ref1
ER  -