Mild Traumatic brain injury (mTBI) or concussive brain injury accounts for approximately 75% of all brain-injured people in United States each year, and is particularly prevalent in contact sports.  Chronic white matter atrophy or degeneration of myelinated axons is a common occurrence after repeated mTBI, which contributes to long-term functional deficits in the patients.  As a major component of white matter tracks, myelin enables fast nerve conduction and provides trophic and metabolic support to the neurons.   Primary demyelination, or loss of myelin in the absence of axonal degeneration and without oligodendrocyte death is frequently observed in mTBI, which is distinct from the cause of myelin loss after moderate to severe TBI.  Myelin loss on intact axons slows nerve conduction resulting in desynchronized neural circuitry.  It also leaves axons more vulnerable to second injury, and in long-term, leads to axonal degeneration and neuronal death.  Therefore, preventing primary myelin loss or promoting remyelination on viable axons may be important in improving neuronal function after mTBI.  This proposal

 

This project focuses on elucidating the molecular mechanisms that contribute to myelin loss associated with mTBI.  In collaboration with Dr. Bryan Pfister at NJIT, we are currently testing the hypothesis that mechanical injury disrupts normal axon-to-oligodendrocyte signaling necessary for maintaining myelin homeostasis in the brain.  We use both in vitro myelinated axon stretch injury model and an in vivo rodent mTBI model to elucidate the signaling mechanism associated with the myelin loss.