a possible role for integrin signaling in diffuse axonal injury一个可能的信号转导在脑弥漫性轴索损伤的作用.pdfVIP

A Possible Role for Integrin Signaling in Diffuse Axonal Injury . . .¤a ¤b Matthew A. Hemphill , Borna E. Dabiri , Sylvain Gabriele , Lucas Kerscher, Christian Franck , Josue A. Goss, Patrick W. Alford¤c, Kevin Kit Parker* Disease Biophysics Group, School of Engineering and Applied Sciences, Wyss Institute of Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts, United States of America Abstract Over the past decade, investigators have attempted to establish the pathophysiological mechanisms by which non- penetrating injuries damage the brain. Several studies have implicated either membrane poration or ion channel dysfunction pursuant to neuronal cell death as the primary mechanism of injury. We hypothesized that traumatic stimulation of integrins may be an important etiological contributor to mild Traumatic Brain Injury. In order to study the effects of forces at the cellular level, we utilized two hierarchical, in vitro systems to mimic traumatic injury to rat cortical neurons: a high velocity stretcher and a magnetic tweezer system. In one system, we controlled focal adhesion formation in neurons cultured on a stretchable substrate loaded with an abrupt, one dimensional strain. With the second system, we used magnetic tweezers to directly simulate the abrupt injury forces endured by a focal adhesion on the neurite. Both systems revealed variations in the rate and nature of neuronal injury as a function of focal adhesion density and direct integrin stimulation without membrane poration. Pha