Acute Blast Injury Reduces Brain Abeta in Two Rodent Species

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.

A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

“…This range includes pressures that were previously reported to produce TBI in rats and mice exposed to head or whole body blasts. 20,21,[24][25][26]30,33 We also measured the pressure detected by the pressure gauge at increasing distances of the tip of the pressure gauge barrel from the gun barrel tip, at a series of blast gun input tank pressure settings, and determined that the blast gun output pressure was uniform over a distance of 3-5 mm from the tip of the blast gun. Accordingly, we measured the pressure waves produced at different peak output blast settings at 4-5-mm from the blast gun tip, and mice were also subsequently positioned at this distance.…”

“…8,[10][11][12][13][14][15][16][17][18] Some researchers have used shock tubes to deliver compressed air blasts to the animal, to mimic blast-produced TBI. [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] These models, however, are often accompanied by hypoxia and blood pressure surges resulting from compression of the lungs, heart, and aorta, which in turn damage brain blood vessels. 8,34 Moreover, the direct exposure of the eye to the blast makes it difficult to distinguish visual deficits caused by brain trauma from visual deficits caused by the direct ocular impact of the blast.…”

Neuronal DNA Methylation Profiling of Blast-Related Traumatic Brain Injury

“…This apparatus has been used in multiple prior studies to deliver blast overpressure injury to rats. 15,20,23,24 Individual rats were anesthetized using an isoflurane gas anesthesia system consisting of a vaporizer, gas lines and valves, and an activated charcoal scavenging system adapted for use with rodents. Rats were placed into a polycarbonate induction chamber, which was closed and immediately flushed with 5% isoflurane mixture in air for 2 min.…”

“…10,11,14,21,22 However, even low-level blast pressure waves are transmitted to the brain and exert a variety of biochemical, pathological, and physiological effects in animals, including the induction of chronic behavioral effects. 3,10,14,[21][22][23][24][25][26][27][28][29] Modulation of gene expression mediated by epigenetic changes, such as deoxyribonucleic acid (DNA) methylation, is one way the brain creates new homeostasis in response to experience, including response to injury. 30 Aberrant regulation of gene expression contributes to long-lasting behavioral abnormalities, where epigenetic modifications serve as a regulatory layer decoding environmental signals into sustained changes in gene expression.…”

Repetitive blast exposure in mice and combat veterans causes persistent cerebellar dysfunction

“…Studies in mice, rats, swine, and other mammals have demonstrated that the intense energy imparted by blast overpressure is sufficient to induce an array of neuropathological and behavioral disturbances (7,(9)(10)(11)(12)(13)(14)(18)(19)(20)(21).…”