Anecdotal observations of blast victims indicate that significant neuropathological and neurobehavioral defects may develop at later stages of life. To pre-clinically model this phenomenon, we have examined neurobehavioral changes in rats up to 1 year after exposure to single and tightly coupled repeated blasts using an advanced blast simulator. Neurobehavioral changes were monitored at acute, sub-acute, and chronic time-points using Morris water maze test of spatial learning and memory, novel object recognition test of short-term memory, open field exploratory activity as a test of anxiety/depression, a rotating pole test for vestibulomotor function, and a rotarod balance test for motor coordination. Single and repeated blasts resulted in significant functional deficits at both acute and chronic time-points. In most functional tests, rats exposed to repeated blasts performed more poorly than rats exposed to single blast. Interestingly, several functional deficits post-blast were most pronounced at 6 months and beyond. Significant neuromotor impairments occurred at early stages after blast exposure and the severity increased with repeated exposures. The novel object recognition testing revealed short-term memory deficits at 6 and 12 months post-blast. The water maze test revealed impairments at acute and chronic stages after blast exposure. The most substantial changes in the blast-exposed rats were observed with the center time and margin time legacies in the open field exploration test at 6, 9, and 12 months post-blast. Notably, these two outcome measures were minimally altered acutely, recovered during sub-acute stages, and were markedly affected during the chronic stages after blast exposures and may implicate development of chronic anxiety and depressive-like behaviors.
In this study, we investigated how animal orientation within a shock tube influences the biomechanical responses of the brain and cerebral vasculature of a rat when exposed to a blast wave. Using three-dimensional finite-element models, we computed the biomechanical responses when the rat was exposed to the same blast-wave overpressure (100 kPa) in a prone (P), vertical (V), or head-only (HO) orientation. We validated our model by comparing the model-predicted and the experimentally measured brain pressures at the lateral ventricle. For all three orientations, the maximum difference between the predicted and measured pressures was 11%. Animal orientation markedly influenced the predicted peak pressure at the anterior position along the mid-sagittal plane of the brain (P = 187 kPa; V = 119 kPa; and HO = 142 kPa). However, the relative differences in the predicted peak pressure between the orientations decreased at the medial (21%) and posterior (7%) positions. In contrast to the pressure, the peak strain in the prone orientation relative to the other orientations at the anterior, medial, and posterior positions was 40-88% lower. Similarly, at these positions, the cerebral vasculature strain in the prone orientation was lower than the strain in the other orientations. These results show that animal orientation in a shock tube influences the biomechanical responses of the brain and the cerebral vasculature of the rat, strongly suggesting that a direct comparison of changes in brain tissue observed from animals exposed at different orientations can lead to incorrect conclusions.
The observed dynamics in polymorphonuclear leukocyte alterations in peripheral blood after OPW exposure were similar to those found recently in clinical observations of nonpenetrating injury and in animal models of infectious insults. Therefore, our data suggest that the main pattern of proinflammatory alterations in the rat model of lung injury induced by exposure to long-duration shock wave is similar to patterns that are characteristic of major trauma. The data further suggest that the expression of polymorphonuclear leukocyte CD11b and the response of iron-transferrin complex can be considered as potential surrogate markers in blood for systemic alterations following OPW-induced injury and, therefore, warrant further investigation in a human pilot study.
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