1G41 衝撃引張ひずみを受ける培養神経細胞の耐性評価

Abstract

Diffuse axonal injury (DAI), being the most common type of pathology in Traumatic Brain Injury (TBI), has two distinct types of axonal pathology; swellings that induced by the neurofilament accumulation as a result of the damaged neurofilament structure in the axonal cytoskeleton and focal compaction and/or impaired transport due to the mechanical insult along the axons fallowed by secondary axotomy, and the axonal bulbs which likely represent complete axonal disconnection. These cytoskeletal abnormalities which proceed to the formation of the swellings and secondary axotomy are the morphological indication of DAI. Although previous researches have provided some insight on understanding the cellular mechanism of neuronal injury, and suggested that the degree of electrophysiological impairment and morphological damage of neurons is directly related to the magnitude and rate of axonal stretch, the exact mechanisms that initiate secondary degeneration in DAI are yet to be fully characterized. Our previous studies suggested that the threshold of dysfunction and interruption of axonal transport is strains of 15-22 % at strain rates of 21-27 s^<-1> and both β-APP and Tau are promising candidates for injury analysis. However, quantitative relation between impulsive strain and axonal injury is yet to be discovered thoroughly. Therefore, in this study, axonal injury induced by uniaxial stretch on differentiated mouse neuronal stem cells in order to clarify the relation between the impulsive strain, strain rate and axonal injury. Herein, evaluation is performed by immunohistochemical labeling, with β-APP and tau protein accumulation as biochemical markers of choice.