Neural Comput - Computer modeling of mild axonal injury: implications for axonal signal transmission.

Tópicos

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Resumo

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.

Resumo Limpo

diffus imag postmortem studi patient mild traumat brain injuri mtbi concuss type consist observ diffus axon injuri white matter axon mechan trauma axon affect properti tetrodotoxinsensit sodium channel node ranvier lead axon degener intraaxon accumul calcium ion activ calcium proteas howev immedi implic axon trauma regard axon function relev transient impair function observ concuss remain elus biophys realist comput model myelin axon develop investig mtbi immedi affect axon function traumat axon show alter signal propag properti nonlinear depend level trauma subthreshold traumat axon decreas spike propag time wherea suprathreshold traumat axon exhibit slowdown spike propag spike propag failur trauma consist reduc axon spike amplitud suscept axon trauma modul function atpdepend sodiumpotassium pump result suggest mechan concuss mtbi lead immedi impair signal propag axon emerg dysfunct neuron inform exchang

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