Tau-ism: The Yin and Yang of Microtubule Sliding, Detachment, and Rupture.

Traumatic brain injury is a nondegenerative, noncongenital insult to the brain caused by external mechanical forces. Recent studies suggest that even mild concussions—if repetitive—can trigger progressive neurological degeneration, a condition that is now widely known as ‘‘chronic traumatic encephalopathy’’ (1). Notably, chronic traumatic encephalopathy continues to progress even decades after the initial insult; the more severe the original injury and the longer the survival, the greater the severity of neurodegeneration. Progressive axonal damage and structural degradation are classic hallmarks of chronic traumatic encephalopathy. Strikingly, these symptoms appear to be shared by a number of other neurodegenerative diseases including Alzheimer’s disease and Parkinsonism. However, the molecular mechanisms of axonal failure remain poorly understood. One of the most common pathological features of traumatic brain injury is diffuse axonal injury (2). To date, the only method to reliably diagnose diffuse axonal injury is post mortem histopathology, where it manifests itself through extensive damage in white-matter tissue. More than half a century ago, experiments with gelatin molds have established that patholog-