Investigation of Blast-induced Neurotrauma in a Rodent models

Abstract

Blast-induced neurotrauma (BINT) has reached critical levels in mordern-day warfare. Explosive devices & other weaponry have become more powerful and devastating in Iraq & Afghanistan wars. In this study, we have sought to elucidate the CNS pathophysiology after varying primary blast overpressures (BOP) by employing two rodents¿ blast injury models where the thoracic region were protected with customized body armour. First model uses a shocktube design and the second uses an open field blast exposure concept. In our study, we observed that varying degree of BOP was able to cause a dose-dependent severities change in the various parameters measured. In short duration, high peak BOP 5g BA animals (~600KPa), the long-term memory and systemic cytokine changes were significantly changed at 2 weeks post-injury. This was in contrast to low BOP, 2g exposure (~240KPa) in which there was neither cognitive dysfunction nor significant systemic inflammation. At higher BOP (open field model), showed more moderate brain injury compared to 5g BA group, indicated by more intense NeuN immunoreactivity with changes in neuronal morphology, increased APP immunoreactivity, microglia activation and early pro-inflammatory cytokines expression in concordance with the temporal changes in histology which persist for longer periods and show signs of lasting changes. In addition, cognitive changes in memory and attention were observed to correspond to histopathological changes observed at similar time-points in the hippocampus and thalamus respectively. The varying degrees of BOP can affect both gray and white matter, as well as the blood-brain-barrier, giving rise to histopathological features that are not only BOP severity-dependent in their immunoreactivity but also in their time course progression. The correlation of the cognitive changes observed in sustained attention and memory with neuronal changes in the thalamus and hippocampus respectively allow us to match brain-specific changes with their function. In conclusion, through the understanding of these molecular changes and relation to cognitive outcome and systemic markers, we have a better grasp on the understanding of BINT. Altogether, the contribution of this data will allow us to interpret changes according to the type of blast injury mechanism, to derive a suitable risk-injury matrix and to use targeted approaches to prevent, mitigate and treat blast CNS injuries in humans in the long run.