Neurogenesis and Oligodendrogenesis in a Mouse Model of Blast-Induced Traumatic Brain Injury

Abstract

Neurological manifestations of blast-induced Post Traumatic Stress Disorder (PTSD) extend long after the initial injury indicating lasting changes in brain function. In this study, we characterized brain injury, changes in neurogenesis and oligodendrogenesis in an adult murine blast model following a short (5 days) and long (21 days) post-blast recovery. Acoustic blasts led to an initial, activation of microglia and astrogliosis and a widespread cortical and subcortical apoptosis. The loss of myelinated cortical axons at 5 days was followed by the reappearance of abnormal misdirected fibers at 21 days. At 21 days post-blast, we observed increases in doublecortin-positive (DCX+ ) neuroblasts in the subventricular zone (SVZ) and hippocampal subgranular zone (SGZ) indicating increased neurogenesis. No changes in DCX+ cells were found in the brain cortex. In the cortex, the early disappearance of myelinated neuronal fibers was accompanied by a loss of O4+ oligodendrocytes and their Ki67-expreasing (Ki67+ ) oligodendrocyte precursor cells (OPC). However, at 5 days we observed a robust appearance of cells expressing Olig2 (O2+ ), an early determinant of oligodendrocyte lineage. At 21 days post-blast, the population of OPC increased and the mature O4+ oligodendrocytes were restored to control levels. In contrast, in the SVZ and SGZ, O4+ cells were not affected by the blast suggesting a local cortical origin for cortical oligodendrogenesis. These results suggest that blast-induced activation of SVZ and SGZ neurogenesis and cortical oligodendrogenesis could have long-lasting impact on brain function including memory disorders observed in both animal models and human’s PTSD.