Behavioral and Myelin-Related Abnormalities after Blast-Induced Mild Traumatic Brain Injury in Mice.

Abstract

In civilian and military settings, mild traumatic brain injury (mTBI) is a common consequence of impacts to the head, sudden blows to the body, and exposure to high-energy atmospheric shockwaves from blast. In some cases, mTBI from blast exposure results in long-term emotional and cognitive deficits and an elevated risk for certain neuropsychiatric diseases. Here, we tested the effects of mTBI on various forms of auditory-cued fear learning and other measures of cognition in male C57BL/6J mice after single or repeated blast exposure (blast TBI; bTBI). bTBI produced an abnormality in the temporal organization of cue-induced freezing behavior in a conditioned trace fear test. Spatial working memory, evaluated by the Y-maze task performance, was also deleteriously affected by bTBI. Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) analysis for glial markers indicated an alteration in the expression of myelin-related genes in the hippocampus and corpus callosum 1-8 weeks after bTBI. Immunohistochemical and ultrastructural analyses detected bTBI-related myelin and axonal damage in the hippocampus and corpus callosum. Together, these data suggest a possible link between blast-induced mTBI, myelin/axonal injury, and cognitive dysfunction.