An In Vitro Uniaxial Stretch Model for Axonal Injury

AbstractWe have developed a unique uniaxial stretching device to study axonal injury and neural cell death resulting from brain tissue deformations common in traumatic head injuries. Using displacement control rather than force control, this device is capable of achieving strains >70% and strain rates up to 90 s-1, well above those currently used for studying axonal injury. We have demonstrated that the deformation of the specimen was uniaxial, uniform and highly reproducible; the prespecified displacement profiles could be realized almost precisely; and adequate cell adhesion could be achieved readily. The entire device can fit into a biological safety cabinet to maintain sterility, and the specimens are convenient for cell culture. This device can be used to investigate a wide range of biomechanical issues involved in diffuse axonal injury. © 2003 Biomedical Engineering Society. PAC2003: 8719La, 8710+e, 8719Rr, 8717–d

[1]  J. Wolf,et al.  Traumatic Axonal Injury Induces Calcium Influx Modulated by Tetrodotoxin-Sensitive Sodium Channels , 2001, The Journal of Neuroscience.

[2]  T A Gennarelli,et al.  Biomechanical analysis of experimental diffuse axonal injury. , 1995, Journal of neurotrauma.

[3]  S. Strich,et al.  SHEARING OF NERVE FIBRES AS A CAUSE OF BRAIN DAMAGE DUE TO HEAD INJURY: A Pathological Study of Twenty Cases , 1961 .

[4]  A. Holbourn MECHANICS OF HEAD INJURIES , 1943 .

[5]  A. Holbourn,et al.  The mechanics of brain injuries , 1945 .

[6]  J. Galbraith,et al.  Axonal structure and function after axolemmal leakage in the squid giant axon. , 1997, Journal of neurotrauma.

[7]  D. Oppenheimer,et al.  Microscopic lesions in the brain following head injury. , 1968, Journal of neurology, neurosurgery, and psychiatry.

[8]  D. Meaney,et al.  Axonal Damage in Traumatic Brain Injury , 2000 .

[9]  L. Thibault,et al.  Mechanical and electrical responses of the squid giant axon to simple elongation. , 1993, Journal of biomechanical engineering.

[10]  J. Povlishock,et al.  A new model for rapid stretch-induced injury of cells in culture: characterization of the model using astrocytes. , 1995, Journal of neurotrauma.

[11]  L. Thibault,et al.  Acute alterations in [Ca2+]i in NG108-15 cells subjected to high strain rate deformation and chemical hypoxia: an in vitro model for neural trauma. , 1996, Journal of neurotrauma.

[12]  Thomas A. Gennarelli,et al.  Diffuse Axonal Injury: An Important Form of Traumatic Brain Damage , 1998 .

[13]  John A. Wolf,et al.  High Tolerance and Delayed Elastic Response of Cultured Axons to Dynamic Stretch Injury , 1999, The Journal of Neuroscience.

[14]  T. Gennarelli Head injury in man and experimental animals: clinical aspects. , 1983, Acta neurochirurgica. Supplementum.

[15]  N. Busis,et al.  Modulation of synapse formation by cyclic adenosine monophosphate. , 1983, Science.

[16]  S. J. Tavalin,et al.  Mechanical perturbation of cultured cortical neurons reveals a stretch-induced delayed depolarization. , 1995, Journal of neurophysiology.

[17]  J. Adams,et al.  Diffuse axonal injury and traumatic coma in the primate , 1982, Annals of neurology.

[18]  J. Weber,et al.  Intracellular Free Calcium Dynamics in Stretch‐Injured Astrocytes , 1998, Journal of neurochemistry.

[19]  E. Ellis,et al.  Effect of Ca2+ on In Vitro Astrocyte Injury , 1997, Journal of neurochemistry.

[20]  T. Gennarelli,et al.  The spectrum of traumatic axonal injury , 1996, Neuropathology and applied neurobiology.

[21]  M. Nirenberg,et al.  A Neuroblastoma × Glioma Hybrid Cell Line with Morphine Receptors , 1974 .

[22]  David F. Meaney,et al.  Mechanical Characterization of an In Vitro Device Designed to Quantitatively Injure Living Brain Tissue , 1998, Annals of Biomedical Engineering.

[23]  T. Gennarelli The Pathobiology of Traumatic Brain Injury , 1997 .

[24]  D F Meaney,et al.  In vitro central nervous system models of mechanically induced trauma: a review. , 1998, Journal of neurotrauma.

[25]  T A Gennarelli,et al.  Neuropathological sequelae of traumatic brain injury: relationship to neurochemical and biomechanical mechanisms. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[26]  L. Satin,et al.  Reduction of Voltage-Dependent Mg2+ Blockade of NMDA Current in Mechanically Injured Neurons , 1996, Science.

[27]  L. Thibault,et al.  Biomechanics of acute subdural hematoma. , 1982, The Journal of trauma.

[28]  J. Povlishock,et al.  Are the Pathobiological Changes Evoked by Traumatic Brain Injury Immediate and Irreversible? , 1995, Brain pathology.

[29]  S. J. Tavalin,et al.  Inhibition of the electrogenic Na pump underlies delayed depolarization of cortical neurons after mechanical injury or glutamate. , 1997, Journal of neurophysiology.

[30]  T A Gennarelli,et al.  Physical model simulations of brain injury in the primate. , 1990, Journal of biomechanics.

[31]  L. Thibault,et al.  Dynamic mechanical deformation of neurons triggers an acute calcium response and cell injury involving the N‐methyl‐D‐aspartate glutamate receptor , 1998, Journal of neuroscience research.