Mild Traumatic Brain Injury

Although mild traumatic brain injury (mTBI) or “concussion” affects over 1 million victims each year in the United States, it is generally ignored as a major health issue.  However, this ‘mild’ form of injury induces persisting neurocognitive dysfunction in many of these patients, exacting an enormous emotional and financial toll on society.  Despite the prevalence and impact of mTBI, little is known about potential anatomic or mechanistic substrates that are reflected by the clinical manifestations.  Nonetheless, there is growing opinion that a mild form of diffuse axonal injury may play a key role in mTBI pathophysiology.  To explore this possibility, we have begun to run parallel studies of mTBI patients compared to a swine model of mTBI induced by head rotational acceleration.  At 2-4 days after injury, conventional MRI showed no abnormalities, but advanced neuroimaging techniques elucidated distinct changes throughout the white matter in both human and swine.  Histopathological examination of the swine brains demonstrated that the signal changes found with neuroimaging correlated with regions of axonal pathology.  In addition, surrogate protein markers of brain pathology were identified after mTBI in the serum of both patients and swine.  A potential mechanism of axon dysfunction and degeneration due to mTBI was elucidated using the swine mTBI model and an in vitro model of mild traumatic axonal injury.  Specifically, we found that dynamic mechanical deformation of axons induces acute sodium channel (NaCh) dysregulation and a chronic NaCh-opathy.  We conclude that mTBI can induce axonal pathology and therefore should not be considered inconsequential.  Indeed, the observation that brain pathology can be detected in mTBI calls for much more extensive efforts to prevent, diagnose and treat mTBI. Supported by NIH grants, NS38104 and NS056202.