An in Vitro Model of Neural Trauma: Device Characterization and Calcium Response to Mechanical Stretch

Geddes, Donna M.; Cargill, Robert S.

doi:10.1115/1.1374201

Cited by 78 publications

(74 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nonetheless, the relative alterations in cell viability following the loading regimes used in this study are consistent with those following both in vivo and in vitro models of neural trauma (Gennarelli et al, 1982;Ellis et al, 1995;Meaney et al, 1995;Ahmed et al, 2000). Strain rate-dependent responses to mechanical loading have previously been reported for neural cells (Ellis et al, 1995;Cargill and Thibault, 1996;LaPlaca et al, 1997;Geddes and Cargill, 2001;LaPlaca et al, 2005), but this is the first report of such a response in neural co-cultures based on 3-D biomechanical inputs.…”

Section: Discussionsupporting

confidence: 63%

Strain rate-dependent induction of reactive astrogliosis and cell death in three-dimensional neuronal–astrocytic co-cultures

2007

View full text Add to dashboard Cite

A mechanical insult to the brain drastically alters the microenvironment as specific cell types become reactive in an effort to sequester severely damaged tissue. Although injury-induced astrogliosis has been investigated, the relationship between well-defined biomechanical inputs and acute astrogliotic alterations are not well understood. We evaluated the effects of strain rate on cell death and astrogliosis using a three-dimensional (3-D) in vitro model of neurons and astrocytes within a bioactive matrix. At 21 days post-plating, co-cultures were deformed to 0.50 shear strain at strain rates of 1, 10, or 30 s −1 . We found that cell death and astrogliotic profiles varied differentially based on strain rate at two days post-insult. Significant cell death was observed after moderate (10 s −1 ) and high (30 s −1 ) rate deformation, but not after quasi-static (1 s −1 ) loading. The vast majority of cell death occurred in neurons, suggesting these cells are more susceptible to high rate shear strains than astrocytes for the insult parameters used here. Injury-induced astrogliosis was compared to co-cultures treated with transforming growth factor β, which induced robust astrocyte hypertrophy and increased glial fibrillary acidic protein (GFAP) and chondroitinsulfate proteoglycans (CSPGs). Quasi-static loading resulted in increased cell density and CSPG secretion. Moderate rate deformation increased cell density, GFAP reactivity, and hypertrophic process density. High rate deformation resulted in increased GFAP reactivity; however, other astrogliotic alterations were not observed at this time-point. These results demonstrate that the mode and degree of astrogliosis depend on rate of deformation, demonstrating astrogliotic augmentation at sub-lethal injury levels as well as levels inducing cell death.

show abstract

Section: Discussionsupporting

confidence: 63%

Strain rate-dependent induction of reactive astrogliosis and cell death in three-dimensional neuronal–astrocytic co-cultures

2007

View full text Add to dashboard Cite

show abstract

“…To accurately model the progression of damage, the constitutive model should be extended to account for the time-dependent behavior of brain tissue. Finally, the injury criterion was based on the stretch of neural axons; however, it has been shown that neural damage is also dependent on the rate of loading (Elkin and Morrison III 2007;Geddes and Cargill 2001;LaPlaca et al 2005). Therefore, in future studies, the effect of strain rate on the functional damage of neural cells should be incorporated into a measure of injury.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, there have been numerous experimental studies aimed at defining injury thresholds for the functional damage of neural cells (Bain and Meaney 2000;Elkin and Morrison III 2007;Geddes and Cargill 2001;Morrison et al 2003;Wolf et al 2001). These injury thresholds are measures of stress or strain at either the cellular or tissue level.…”

Section: Axonal Strain Injury Criterionmentioning

confidence: 99%

An axonal strain injury criterion for traumatic brain injury

Wright¹,

Ramesh²

2011

Biomech Model Mechanobiol

150

165

View full text Add to dashboard Cite

Computational models are often used as tools to study traumatic brain injury. The fidelity of such models depends on the incorporation of an appropriate level of structural detail, the accurate representation of the material behavior, and the use of an appropriate measure of injury. In this study, an axonal strain injury criterion is used to estimate the probability of diffuse axonal injury (DAI), which accounts for a large percentage of deaths due to brain trauma and is characterized by damage to neural axons in the deep white matter regions of the brain. We present an analytical and computational model that treats the white matter as an anisotropic, hyperelastic material. Diffusion tensor imaging is used to incorporate the structural orientation of the neural axons into the model. It is shown that the degree of injury that is predicted in a computational model of DAI is highly dependent on the incorporation of the axonal orientation information and the inclusion of anisotropy into the constitutive model for white matter.

show abstract

“…Using lactate dehydrogenase (LDH) release or highmolecular-weight tracer uptake to evaluate membrane damage in various TBI models, our laboratory and others have established that membrane disruption can occur at the moment of injury, suggesting that the traumatic event evokes direct mechanical poration of the neuronal cell membrane (Pettus et al, 1994;LaPlaca et al, 1997;Geddes and Cargill, 2001;Geddes et al, 2003;Singleton and Povlishock, 2004). In these studies, it was suggested that the altered neuronal membrane permeability generated ionic disturbances to precipitate cell death.…”

Section: Membrane Disruption and Enduring Membrane Permeabilitymentioning

confidence: 99%

Mechanoporation Induced by Diffuse Traumatic Brain Injury: An Irreversible or Reversible Response to Injury?

Farkas¹,

Lifshitz²,

Povlishock³

2006

J. Neurosci.

164

149

View full text Add to dashboard Cite

Diffuse traumatic brain injury (DTBI) is associated with neuronal plasmalemmal disruption, leading to either necrosis or reactive change without cell death. This study examined whether enduring membrane perturbation consistently occurs, leading to cell death, or if there is the potential for transient perturbation followed by resealing/recovery. We also examined the relationship of these events to calpainmediated spectrin proteolysis (CMSP). To assess plasmalemmal disruption, rats (n ϭ 21) received intracerebroventricular infusion 2 h before DTBI of a normally excluded 10 kDa fluorophore-labeled dextran. To reveal plasmalemmal resealing or enduring disruption, rats were infused with another labeled dextran 2 h (n ϭ 10) or 6 h (n ϭ 11) after injury. Immunohistochemistry for the 150 kDa spectrin breakdown product evaluated the concomitant role of CMSP. Neocortical neurons were followed with confocal and electron microscopy.

show abstract

An in Vitro Model of Neural Trauma: Device Characterization and Calcium Response to Mechanical Stretch

Cited by 78 publications

References 26 publications

Strain rate-dependent induction of reactive astrogliosis and cell death in three-dimensional neuronal–astrocytic co-cultures

Strain rate-dependent induction of reactive astrogliosis and cell death in three-dimensional neuronal–astrocytic co-cultures

An axonal strain injury criterion for traumatic brain injury

Mechanoporation Induced by Diffuse Traumatic Brain Injury: An Irreversible or Reversible Response to Injury?

Contact Info

Product

Resources

About