PMID- 24726403 OWN - NLM STAT- MEDLINE DCOM- 20141201 LR - 20140520 IS - 1872-7972 (Electronic) IS - 0304-3940 (Linking) VI - 570 DP - 2014 Jun 6 TI - Hippocampal vulnerability and subacute response following varied blast magnitudes. PG - 33-7 LID - S0304-3940(14)00271-7 [pii] LID - 10.1016/j.neulet.2014.03.072 [doi] AB - Clinical outcomes from blast neurotrauma are associated with higher order cognitive functions such as memory, problem solving skills and attention. Current literature is limited to a single overpressure exposure or repeated exposures at the same level of overpressure and is focused on the acute response (<3 days). In an attempt to expand the understanding of neuropathological and molecular changes of the subacute response (7 days post injury), we used an established rodent model of blast neurotrauma. Three pressure magnitudes (low, moderate and high) were used to evaluate molecular injury thresholds. Immunohistochemical analysis demonstrated increased cleaved caspase-3 levels and loss of neuronal population (NeuN+) within the hippocampus of all pressure groups. On the contrary, selective activation of microglia was observed in the low blast group. In addition, increased astrocytes (GFAP), membrane signal transduction protein (Map2k1) and calcium regulator mechanosensitive protein (Piezo 2) were observed in the moderate blast group. Results from gene expression analysis suggested ongoing neuroprotection, as brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF) and Mn and CuZn superoxide dismutases (SOD) all increased in the low and moderate blast groups. Ongoing neuroprotection was further supported by increased SOD levels observed in the moderate group using immunohistochemistry. The gene expression level of glutamate aspartate transporter (GLAST) was upregulated in the low, but downregulated in the high blast group, while no changes were found in the moderate group. Overall, the data shown here provides evidence of a diverse neuroprotective and glial response to various levels of blast exposure. This mechanistic role of neuroprotection is vital in understanding ongoing cellular stress, both at the gene and protein levels, in order to develop interventional studies for the prognosis of injury. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Sajja, Venkata Siva Sai Sujith AU - Sajja VS AD - School of Biomedical Engineering and Sciences, Virginia Polytechnic and State University, Blacksburg, VA, USA. Electronic address: sujith.srm@gmail.com. FAU - Ereifej, Evon S AU - Ereifej ES AD - School of Biomedical Engineering and Sciences, Virginia Polytechnic and State University, Blacksburg, VA, USA. FAU - VandeVord, Pamela J AU - VandeVord PJ AD - School of Biomedical Engineering and Sciences, Virginia Polytechnic and State University, Blacksburg, VA, USA; Salem VA Medical Center, Research & Development Service, Salem, VA, USA. Electronic address: pvord@vt.edu. LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20140412 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Interleukin-3) RN - 0 (Receptors, Glutamate) SB - IM MH - Animals MH - Blast Injuries/*metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Head Injuries, Closed/*metabolism MH - Hippocampus/*metabolism MH - Inflammation/metabolism MH - Interleukin-3/metabolism MH - Male MH - Oxidative Stress MH - Pressure MH - Rats, Sprague-Dawley MH - Receptors, Glutamate/metabolism MH - Signal Transduction OTO - NOTNLM OT - Blast OT - Hippocampus OT - Magnitude OT - Oxidative stress OT - Piezo2 EDAT- 2014/04/15 06:00 MHDA- 2014/12/15 06:00 CRDT- 2014/04/15 06:00 PHST- 2014/01/16 00:00 [received] PHST- 2014/03/27 00:00 [revised] PHST- 2014/03/28 00:00 [accepted] PHST- 2014/04/15 06:00 [entrez] PHST- 2014/04/15 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] AID - S0304-3940(14)00271-7 [pii] AID - 10.1016/j.neulet.2014.03.072 [doi] PST - ppublish SO - Neurosci Lett. 2014 Jun 6;570:33-7. doi: 10.1016/j.neulet.2014.03.072. Epub 2014 Apr 12.