Suchergebnisse

The incidence of traumatic brain injury (TBI) among military personnel is at its highest point in U.S. history. Experimental animal models of blast have provided a wealth of insight into blast injury. The mechanisms of neurotrauma caused by blast, however, are still under debate. Specifically, it is unclear whether the blast shockwave in the absence of head motion is sufficient to induce brain trauma. In this study, the consequences of blast injury were investigated in a rat model of primary blast TBI. Animals were exposed to blast shockwaves with peak reflected overpressures of either 100 or 450 kPa (39 and 110 kPa incident pressure, respectively) and subsequently underwent a battery of behavioral tests. Diffusion tensor imaging (DTI), a promising method to detect blast injury in humans, was performed on fixed brains to detect and visualize the spatial dependence of blast injury. Blast TBI caused significant deficits in memory function as evidenced by the Morris Water Maze, but limited emotional deficits as evidenced by the Open Field Test and Elevated Plus Maze. Fractional anisotropy, a metric derived from DTI, revealed significant brain abnormalities in blast-exposed animals. A significant relationship between memory deficits and brain microstructure was evident in the hippocampus, consistent with its role in memory function. The results provide fundamental insight into the neurological consequences of blast TBI, including the evolution of injury during the sub-acute phase and the spatially dependent pattern of injury. The relationship between memory dysfunction and microstructural brain abnormalities may provide insight into the persistent cognitive difficulties experienced by soldiers exposed to blast neurotrauma and may be important to guide therapeutic and rehabilitative efforts.

Due to recent involvement in military conflicts, and an increase in the use of explosives, there has been an escalation in the incidence of blast-induced traumatic brain injury (bTBI) among US military personnel. Having a better understanding of the cellular and molecular cascade of events in bTBI is prerequisite for the development of an effective therapy that currently is unavailable. The present study utilized organotypic hippocampal slice cultures (OHCs) exposed to blast overpressures of 150 kPa (low) and 280 kPa (high) as an in vitro bTBI model. Using this model, we further characterized the cellular effects of the blast injury. Blast-evoked cell death was visualized by a propidium iodide (PI) uptake assay as early as 2 h post-injury. Quantification of PI staining in the cornu Ammonis 1 and 3 (CA1 and CA3) and the dentate gyrus regions of the hippocampus at 2, 24, 48, and 72 h following blast exposure revealed significant time dependent effects. OHCs exposed to 150 kPa demonstrated a slow increase in cell death plateauing between 24 and 48 h, while OHCs from the high-blast group exhibited a rapid increase in cell death already at 2 h, peaking at ~24 h post-injury. Measurements of lactate dehydrogenase release into the culture medium also revealed a significant increase in cell lysis in both low- and high-blast groups compared to sham controls. OHCs were fixed at 72 h post-injury and immunostained for markers against neurons, astrocytes, and microglia. Labeling OHCs with PI, neuronal, and glial markers revealed that the blast-evoked extensive neuronal death and to a lesser extent loss of glial cells. Furthermore, our data demonstrated activation of astrocytes and microglial cells in low- and high-blasted OHCs, which reached a statistically significant difference in the high-blast group. These data confirmed that our in vitro bTBI model is a useful tool for studying cellular and molecular changes after blast exposure.