Mild traumatic brain injury in the rat alters neuronal number in the limbic system and increases conditioned fear and anxiety-like behaviors

Recent reports suggest that experiencing a mild closed head trauma or mild traumatic brain injury (mTBI) is associated with a greater incidence of anxiety disorders. Dysfunction of limbic structures, such as the medial prefrontal cortex, amygdala and hippocampus, is associated with the symptoms of anxiety disorders. Therefore, the goal of the current studies was to characterize the consequences of closed mTBI on these limbic structures and associated fear and anxiety-related behaviors. A weight-drop procedure was employed to induce mTBI in male rats. Rats were transcardically perfused 4 or 9. days following exposure to mTBI or control procedures, and neuronal number, brain region area, and the number of apoptotic cells in each region were determined. In separate groups of rats, the effects of mTBI on anxiety-like behaviors, motor function, nociception, and acquisition, retention and extinction of contextual fear were also assessed. Findings suggest that mTBI was associated with significant neuronal cell loss in the CA1 region of the dorsal hippocampus and increased cell number in subregions of the amygdala, both of which appear to be related to alterations to apoptosis in these regions following mTBI. Furthermore, mTBI increased expression of anxiety-like behaviors and conditioned fear, with no effect on motor performance or nociception. Overall, a single impact to the skull to mimic mTBI in rats produces discrete alterations to neuronal numbers within the limbic system and specific emotional deficits, providing a potential neurobiological link between mTBI and anxiety disorders.