Transient cognitive deficits are associated with the reversible accumulation of amyloid precursor protein after mild traumatic brain injury.

Mild traumatic brain injury (MTBI) may frequently cause transient behavioral abnormalities without observable morphological findings. In this study, we investigated neuropathological mechanisms underlying transient cognitive deficits after MTBI. Mongolian gerbils were subjected to experimental MTBI. At various time points after injury, behavioral changes were evaluated by the open-field test and T-maze test, and immunohistochemistry of microtubule-associated protein (MAP2) and amyloid precursor protein (APP) was performed to examine disruptions of the neuronal cytoskeleton and axonal transport, respectively. Transient cognitive deficits were observed after MTBI. Sustained MAP2 loss was found within the cortical impact site, but not the hippocampus. Transient APP accumulation at the same time as transient cognitive deficits occurred in the ipsilateral hemisphere, particularly in the subcortical white matter. These results suggest that the axonal dysfunction indicated by the reversible APP accumulation in the white matter, but not the sustained neuronal cytoskeletal damage reflected by the cortical MAP2 loss confined to the impact site, is responsible for the transient functional deficits after MTBI.