Acute alterations in [Ca2+]i in NG108-15 cells subjected to high strain rate deformation and chemical hypoxia: an in vitro model for neural

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Cargill, II, Robert S.¹; Thibault, Lawrence E.^1,2

Acute alterations in [Ca²⁺]_i in NG108-15 cells subjected to high strain rate deformation and chemical hypoxia: an in vitro model for neural

J Neurotrauma. July 1996;13(7):395-407

Affiliations

¹Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104

²Current address: Bioengineering & Biomechanics, Medical College of Philadelphia/Hahnemann University, Department of Neurosurgery, Broad and Vine Sts., Mail stop 455, Philadelphia, PA 19102-1192
Abstract

The short-term (less than 2 min) alterations in the intracellular free calcium concentration in differentiated NG108-15 (neuroblastoma cross glioma) cells exposed to dynamic mechanical deformation with and without superimposed chemical hypoxia were determined. A previously developed device, modified for these studies, was used to apply deformations at a magnitude and rate representative of those experienced by neural tissue in Traumatic Brain Injury. Chemical hypoxia was imposed using a combination of 2-deoxy-d-glucose and salicylate, anaerobic and aerobic metabolic blockers, respectively. Real time measurement of intracellular free calcium concentration using Fura-2 and a custom epifluorescence microscopy system provided a quantitative index of cell response. At high rates of deformation (∼10 sec^-1), increases in intracellular free calcium concentration were exponentially related to the magnitude of the applied deformation. Chemical hypoxia had no effect on this acute response. At low rates of deformation, small increases in intracellular free calcium concentration were independent of the magnitude of the deformation. These findings indicate that strategies for reducing severity of TBI should focus on minimizing the rate of deformation of neural cells. Together with data from animal, physical, and finite element models, these data can be employed in the development of physiologic injury tolerance criteria for the whole head.
Links

DOI: 10.1089/neu.1996.13.395

PubMed: 8863195

WoS: A1996VB73200005

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2003	Morrison B III, Cater HL, Wang CC-B, Thomas FC, Hung CT, Ateshian GA, Sundstrom LE. A tissue level tolerance criterion for living brain developed with an in vitro model of traumatic mechanical loading. Stapp Car Crash J. 2003;47:93-105. SAE 2003-22-0006.
1997	LaPlaca MC, Thibault LE. Anin vitro traumatic injury model to examine the response of neurons to a hydrodynamically-induced deformation. Ann Biomed Eng. July 1997;25(4):665-677.
2005	LaPlaca MC, Cullen DK, McLoughlin JJ, Cargill RS II. High rate shear strain of three-dimensional neural cell cultures: a new in vitro traumatic brain injury model. J Biomech. May 2005;38(5):1093-1105.
2006	Cater HL, Sundstrom LE, Morrison B III. Temporal development of hippocampal cell death is dependent on tissue strain but not strain rate. J Biomech. 2006;39(16):2810-2818.
2000	Morrison B III, Meaney DF, Margulies SS, McIntosh TK. Dynamic mechanical stretch of organotypic brain slice cultures induces differential genomic expression: relationship to mechanical parameters. J Biomech Eng. June 2000;122(3):224-230.
2001	Geddes DM, Cargill RS II. An in vitro model of neural trauma: device characterization and calcium response to mechanical stretch. J Biomech Eng. June 2001;123(3):247-255.
2006	Morrison B III, Cater HL, Benham CD, Sundstrom LE. An in vitro model of traumatic brain injury utilising two-dimensional stretch of organotypic hippocampal slice cultures. J Neurosci Meth. 2006;150(2):192-201.
1997	LaPlaca MC, Lee VM-Y, Thibault LE. An in vitro model of traumatic neuronal injury: loading rate-dependent changes in acute cytosolic calcium and lactate dehydrogenase release. J Neurotrauma. June 1997;14(5):355-368.
1998	Morrison B III, Saatman KE, Meaney DF, McIntosh TK. In vitro central nervous system models of mechanically induced trauma: a review. J Neurotrauma. November 1998;15(11):911-928.
2003	Geddes DM, Cargill RS II, LaPlaca MC. Mechanical stretch to neurons results in a strain rate and magnitude-dependent increase in plasma membrane permeability. J Neurotrauma. October 2003;20(10):1039-1049.
2006	Geddes-Klein DM, Schiffman KB, Meaney DF. Mechanisms and consequences of neuronal stretch injury in vitro differ with the model of trauma. J Neurotrauma. February 2006;23(2):193-204.
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2003	Serbest G. In Vitro Neuronal Cell Injury Model: Characterization and Treatment Strategies [PhD thesis]. Drexel University; July 2003.
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2014	Dastgheyb RM. Mechanisms of Axonal Pathology in the Context of Traumatic Brain Injury [PhD thesis]. Drexel University; November 2014.
2002	Geddes DM. Selective Vulnerability of Hippocampal Vs. Cortical Neurons to Mechanically Induced Increases in Plasma Membrane Permeability [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; February 2002.
2004	Prado GR. Neuronal Plasma Membrane Disruption in Traumatic Brain Injury [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; July 2004.
2005	Cullen DK. Traumatically-Induced Degeneration and Reactive Astrogliosis in Three-Dimensional Neural Co-Cultures: Factors Influencing Neural Stem Cell Survival and Integration [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; December 2005.
2011	Wester B. Development and Characterization of Mechanically Actuated Microtweezers for Use in a Single-Cell Neural Injury Model [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; May 2011.
2007	Hao H. Identification of the Effects of Axonal Coupling to the Glial Matrix on Axonal Kinematics [PhD thesis]. Rutgers University; October 2007.
2004	Sparrey CJ. The Effect of Impact Velocity on Acute Spinal Cord Injury [Master's thesis]. Vancouver, BC: University of British Columbia; July 2004.
2014	Patton DA. The Biomechanical Determinants of Sports-Related Concussion: Finite Element Simulations of Unhelmeted Head Impacts to Evaluate Kinematic and Tissue-Level Predictors of Injury and Investigate the Design Implications for Soft-Shell Headgear [PhD thesis]. University of New South Wales; March 2014.
1996	LaPlaca MC. Deformation Response and Cytosolic Calcium Increases in NTera2 Neurons Subjected to Traumatic Levels of Hydrodynamic Shear Stress [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 1996.
1997	Goldstein DM. In Vitro and Mathematical Models of the Injury Response of Axons to Dynamic Loading of the Central Nervous System [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 1997.
1998	Blackman BR. Endothelial Cell Response to Controlled Loading Rates of Hydrodynamically-Applied Shear Stress [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 1998.
1999	Morrison B III. Differential Genomic Expression After Mechanical Injury of Organotypic Brain Slice Cultures: An in Vitro Model of Traumatic Brain Injury [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 1999.