IMPROVING NEUROREGENERATION AFTER EXPOSURES TO MULTIPLE MILD BLASTS

Repeated exposures to low levels of explosive blast are a significant health issue in the US military because they can lead to chronic neurobehavioral abnormalities, including mood and anxiety disorders and memory impairments. We have developed a rodent model to mimic repeated exposures to mild blast and analyzed the behavioral, cellular and molecular outcomes. We are also testing the effect of a ¿rest¿ period between sets of blast exposures on these outcomes. Here we report that exposures of rats to multiple mild level of blast overpressure results in: a) changes vital parameters; b) changes in the expression of protein markers in the hippocampus and c) decreased de novo hippocampal neurogenesis. Altered vital parameters in response to blasts include arterial O2 saturation and heart rate whereas pulse distension and breath rate were minimally or not affected. Proteomics analysis of brain regions that are parts of the anxiety and memory circuitries (prefrontal cortex, amygdala, dorsal and ventral hippocampus) showed elevated expression of the selected markers even after exposure to a single blast. However, there are candidate markers that appear to respond specifically to multiple blasts. While exposure to a single blast increased DCX immunoreacitvity in the hippocampus, exposures to multiple blasts resulted in decreased DCX immunoreacitvity suggesting that de novo hippocampal neurogenesis is down-regulated by multiple exposures. In summary, the observed changes in vital parameters, protein expressions and de novo hippocampal neurogenesis can contribute to the observed neurobehavioral abnormalities, predominantly increased anxiety and memory impairments observed after exposures to multiple mild blasts.