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Temporal development of hippocampal cell death is dependent on tissue strain but not strain rate

Temporal development of hippocampal cell death is dependent on tissue strain but not strain rate
Temporal development of hippocampal cell death is dependent on tissue strain but not strain rate
Deformation of brain tissue in response to mechanical loading of the head is the root-cause of traumatic brain injury (TBI). Even below ultimate failure limits, deformation activates pathophysiological cascades resulting in delayed cell death. Injury response of soft tissues, such as the chest and spinal cord, is dependent on the product of deformation and velocity, a parameter termed the viscous criterion. We set out to test if hippocampal cell death could be predicted by a similar combination of strain and strain rate and if the viscous criterion was valid for hippocampus. Quantitative prediction of the brain's biological response to mechanical stimuli is difficult to achieve in animal models of TBI, so we utilized an in vitro model of TBI based on hippocampal slice cultures. We quantified the temporal development of cell death after precisely controlled deformations for 30 combinations of strain (0.05-0.50) and strain rate (0.1-50 s(-1)) relevant to TBI. Loading conditions for a subset of cultures were verified by analysis of highspeed video. Cell death was found to be significantly dependent on time-post injury, on strain magnitude, and to a lesser extent, on anatomical region by a repeated-measures, three-way ANOVA. The responses of the CA1 and CA3 regions of the hippocampus were not statistically different in contrast to some in vivo TBI studies. Surprisingly, cell death was not dependent on strain rate leading us to conclude that the viscous criterion is not a valid predictor for hippocampal tissue injury. Given the large data set and extensive combinations of biomechanical parameters, predictive mathematical functions relating independent variables (strain, region, and time post-injury) to the resultant cell death were defined. These functions can be used as tolerance criteria to equip finite element models of TBI with the added capability to predict biological consequences.
tolerance criterion, brain injury, in vivo, astrocytes, brain-injury, repair, slice cultures, neuronal survival, failure, dynamic cortical deformation, diffuse axonal injury, vitro model, tolerance criteria, hippocampus, model, mechanical stretch, viscous criterion, in-vitro model, tissues, calcium response, axonal injury, injuries, brain, in-vivo, traumatic brain injury
0021-9290
2810-2818
Cater, Heather L.
39c5b10e-e778-4d54-ab5e-29d76b82c343
Sundstrom, Lars E.
bb62018d-0157-4274-a865-448ed12934bd
Morrison, Barclay
97d2b4dc-0ce1-4706-a0ee-bb3ce7733f22
Cater, Heather L.
39c5b10e-e778-4d54-ab5e-29d76b82c343
Sundstrom, Lars E.
bb62018d-0157-4274-a865-448ed12934bd
Morrison, Barclay
97d2b4dc-0ce1-4706-a0ee-bb3ce7733f22

Cater, Heather L., Sundstrom, Lars E. and Morrison, Barclay (2006) Temporal development of hippocampal cell death is dependent on tissue strain but not strain rate. Journal of Biomechanics, 39 (15), 2810-2818. (doi:10.1016/j.jbiomech.2005.09.023).

Record type: Article

Abstract

Deformation of brain tissue in response to mechanical loading of the head is the root-cause of traumatic brain injury (TBI). Even below ultimate failure limits, deformation activates pathophysiological cascades resulting in delayed cell death. Injury response of soft tissues, such as the chest and spinal cord, is dependent on the product of deformation and velocity, a parameter termed the viscous criterion. We set out to test if hippocampal cell death could be predicted by a similar combination of strain and strain rate and if the viscous criterion was valid for hippocampus. Quantitative prediction of the brain's biological response to mechanical stimuli is difficult to achieve in animal models of TBI, so we utilized an in vitro model of TBI based on hippocampal slice cultures. We quantified the temporal development of cell death after precisely controlled deformations for 30 combinations of strain (0.05-0.50) and strain rate (0.1-50 s(-1)) relevant to TBI. Loading conditions for a subset of cultures were verified by analysis of highspeed video. Cell death was found to be significantly dependent on time-post injury, on strain magnitude, and to a lesser extent, on anatomical region by a repeated-measures, three-way ANOVA. The responses of the CA1 and CA3 regions of the hippocampus were not statistically different in contrast to some in vivo TBI studies. Surprisingly, cell death was not dependent on strain rate leading us to conclude that the viscous criterion is not a valid predictor for hippocampal tissue injury. Given the large data set and extensive combinations of biomechanical parameters, predictive mathematical functions relating independent variables (strain, region, and time post-injury) to the resultant cell death were defined. These functions can be used as tolerance criteria to equip finite element models of TBI with the added capability to predict biological consequences.

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More information

Published date: 2006
Keywords: tolerance criterion, brain injury, in vivo, astrocytes, brain-injury, repair, slice cultures, neuronal survival, failure, dynamic cortical deformation, diffuse axonal injury, vitro model, tolerance criteria, hippocampus, model, mechanical stretch, viscous criterion, in-vitro model, tissues, calcium response, axonal injury, injuries, brain, in-vivo, traumatic brain injury

Identifiers

Local EPrints ID: 62350
URI: https://eprints.soton.ac.uk/id/eprint/62350
ISSN: 0021-9290
PURE UUID: 7c6be69c-e062-4bd6-a8ac-3fb4830ad990

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Date deposited: 12 Sep 2008
Last modified: 13 Mar 2019 20:27

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