Neuropathology and neurobehavioral alterations in a rat model of traumatic brain injury to occupants of vehicles targeted by underbody blasts

Abstract

Many victims of blast-induced traumatic brain injury are occupants of military vehicles targeted by land mines. Recently improved vehicle designs protect these individuals against blast overpressure, leaving acceleration as the main force potentially responsible for brain injury. We recently developed a unique rat model of under-vehicle blast-induced hyperacceleration where exposure to acceleration as low as 50G force results in histopathological evidence of diffuse axonal injury and astrocyte activation, with no evidence of neuronal cell death. This study investigated the effects of much higher blast-induced accelerations (1200 to 2800G) on neuronal cell death, neuro-inflammation, behavioral deficits and mortality. Adult male rats were subjected to this range of accelerations, in the absence of exposure to blast overpressure, and evaluated over 28days for working memory (Y maze) and anxiety (elevated plus maze). In addition, brains obtained from rats at one and seven days post-injury were used for neuropathology and neurochemical assays. Sixty seven percent of rats died soon after being subjected to blasts resulting in 2800G acceleration. All rats exposed to 2400G acceleration survived and exhibited transient deficits in working memory and long-term anxiety like behaviors, while those exposed to 1200 acceleration G force only demonstrated increased anxiety. Behavioral deficits were associated with acute microglia/macrophage activation, increased hippocampal neuronal death, and reduced levels of tight junction- and synapse- associated proteins. Taken together, these results suggest that exposure of rats to high underbody blast-induced G forces results in neurologic injury accompanied by neuronal apoptosis, neuroinflammation and evidence for neurosynaptic alterations.

Modeling the Long-Term Consequences of Repeated Blast-Induced Mild Traumatic Brain Injuries

“…[42][43][44][45] Underbody explosions, frequent in combat and patrol situations, create heterogeneous physical forces of which hyperacceleration of the body and/or ejecta is an important component. 46,47 Another combat-relevant scenario: explosion taking place within a walled structure (e.g., house or building). Explosions within walled structures create an extremely complex blast environment because pressure waves are reflected from walls, the floor, and other surfaces, thereby exposing subjects to highly variable waveforms of differing intensities.…”

Temporal Sequences of Synapse Disintegration Triggered by Afferent Axon Transection, Time-Lapse Imaging Study of Presynaptic and Postsynaptic Molecules

“…Spines and postsynaptic sites also decrease in animal models of TBI (Wakade et al, 2010; Campbell et al, 2012; Winston et al, 2013; Tchantchou et al, 2017), but simultaneous damage to both presynaptic axons and postsynaptic neurons could not be distinguished in animal models of TBI (Gao et al, 2011; Gao and Chen, 2011). Also, the contribution of glial cells, which are in close contact with neuronal components, especially synaptic structures, should be considered in TBI models (Eroglu and Barres, 2010).…”

“…In TBI, axons are subjected to mechanical damage and these damaged axons subsequently undergo the process of Wallerian degeneration (Armstrong et al, 2016). Also, the numbers of synaptophysin clusters and synaptophysin expression level has been reported to decrease in animal models of TBI (Thompson et al, 2006; Tchantchou et al, 2017). Our afferent elimination procedure performed in culture was able to reduce the number of presynaptic sites by mechanical axonal injury and induce axonal degeneration (Fig.…”

Rat Model of Brain Injury to Occupants of Vehicles Targeted by Land Mines: Mitigation by Elastomeric Frame Designs

“…Seventy percent of rats exposed to 2850g died soon thereafter, whereas all rats exposed to 2400g survived, but demonstrated evidence for a transient deficit in working memory, chronic anxiety, and neuropathology. 6 In these experiments, only a thin, 0.6 cm rubber pad was located between the top and bottom platforms, which dampened oscillations, but had no significant effect on the maximum transmission of force between the two plates.…”