Abstract
Blast-induced traumatic brain injury (TBI) has been a major cause of morbidity and mortality in the conflicts in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. In particular, it is unclear whether blast injures the brain through mechanisms similar to those found in non-blast closed impact injuries (nbTBI). The β-amyloid (Aβ) peptide associated with the development of Alzheimer’s disease is elevated acutely following TBI in humans as well as in experimental animal models of nbTBI. We examined levels of brain Aβ following experimental blast injury using enzyme-linked immunosorbent assays for Aβ 40 and 42. In both rat and mouse models of blast injury, rather than being increased, endogenous rodent brain Aβ levels were decreased acutely following injury. Levels of the amyloid precursor protein (APP) were increased following blast exposure although there was no evidence of axonal pathology based on APP immunohistochemical staining. Unlike the findings in nbTBI animal models, levels of the β-secretase, β-site APP cleaving enzyme 1, and the γ-secretase component presenilin-1 were unchanged following blast exposure. These studies have implications for understanding the nature of blast injury to the brain. They also suggest that strategies aimed at lowering Aβ production may not be effective for treating acute blast injury to the brain.
Highlights
Blast-induced brain injury has been of longstanding interest in military head trauma (Jones et al, 2007)
WESTERN BLOTTING Protein samples (Triton X-100 extracts for amyloid precursor protein (APP) and BACE1; SDS extracts for presenilin-1) were separated by SDS-PAGE and blotted onto polyvinylidene difluoride (PVDF) membranes (Millipore Corporation, Billerica, MA, USA)
Two body orientations were tested with the rats facing toward or sideways to the blast wave with the head and body fixed in a plastic restraint cone to restrict movement
Summary
Blast-induced brain injury has been of longstanding interest in military head trauma (Jones et al, 2007). Blast exposure reduces brain abeta (BACE1), the principal β-secretase (Blasko et al, 2004; Chen et al, 2004; Nadler et al, 2008; Loane et al, 2009; Zohar et al, 2011) These observations are all consistent with increased processing of APP (producing increased Aβ) after TBI. All prior studies examining Aβ levels in experimental animals have been performed using models that mimic the types of contusional and diffuse brain injuries associated with nbTBI closed impact head injury (Abrahamson et al, 2009; Loane et al, 2009, 2011; Schwetye et al, 2010; Tran et al, 2011; Tian et al, 2012; Yu et al, 2012; Zhang et al, 2012). We took advantage of the availability of this tissue to examine levels of brain Aβ following experimental blast injury
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