Computer modeling of mild axonal injury: implications for axonal signal transmission

Diffusion imaging and postmortem studies of patients with mild traumatic brain injury (mTBI) of the concussive type are consistent with the observations of diffuse axonal injury to the white matter axons. Mechanical trauma to axons affects the properties of tetrodotoxin-sensitive sodium channels at the nodes of Ranvier, leading to axonal degeneration through intra-axonal accumulation of calcium ions and activation of calcium proteases; however, the immediate implications of axonal trauma regarding axonal functionality and their relevance to transient impairment of function as observed in concussion remain elusive. A biophysically realistic computational model of a myelinated axon was developed to investigate how mTBI could immediately affect axonal function. Traumatized axons showed alterations in signal propagation properties that nonlinearly depended on the level of trauma; subthreshold traumatized axons had decreased spike propagation time, whereas suprathreshold traumatized axons exhibited a slowdown of spike propagation and spike propagation failure. Trauma had consistently reduced axonal spike amplitude. The susceptibility of an axon to trauma could be modulated by the function of an ATP-dependent sodium-potassium pump. The results suggest a mechanism by which concussive mTBI could lead to the immediate impairment of signal propagation through the axon and the emerging dysfunctional neuronal information exchange.