Abstract
The US population suffers 1.5 million head injuries annually, of which mild traumatic brain injuries (mTBI) comprise 75%. Many individuals subsequently experience long-lasting negative symptoms, including anxiety. Previous rat-based work in our laboratory has shown that mTBI changes neuronal counts in the hippocampus and amygdala, regions associated with anxiety. Specifically, mTBI increased neuronal death in the dorsal CA1 sub-region of the hippocampus, but attenuated it in the medial (MeA) and the basolateral nuclei of the amygdala nine days following injury, which was associated with greater anxiety. We have also shown that glucocorticoid receptor (GR) antagonism prior to concomitant stress and mTBI extinguishes anxiety-like behaviors. Using immunohistochemistry, this study examines the expression of brain-derived neurotrophic factor (BDNF) following social defeat and mTBI, and whether this is affected by prior glucocorticoid receptor antagonism as a potential mechanism behind these anxiety and neuronal differences. Here, stress and mTBI upregulate BDNF in the MeA, and both GR and mineralocorticoid receptor antagonism downregulate BDNF in the dorsal hippocampal CA1 and dentate gyrus, as well as the central nucleus of the amygdala. These findings suggest BDNF plays a role in the mechanism underlying neuronal changes following mTBI in amygdalar and hippocampal subregions, and may participate in stress elicited changes to neural plasticity in these regions. Taken together, these results suggest an essential role for BDNF in the development of anxiety behaviors following concurrent stress and mTBI.