High rate shear strain of three-dimensional neural cell cultures: a new in vitro traumatic brain injury model

LaPlaca, Michelle C.; Cullen, D. Kacy; McLoughlin, Justin J.; Cargill, Robert S.

doi:10.1016/j.jbiomech.2004.05.032

Cited by 194 publications

(164 citation statements)

References 40 publications

Supporting

Mentioning

158

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: 85%

“…The strain rates chosen for this study ranged from sub-lethal to severe levels (LaPlaca et al, 2005;Cullen and LaPlaca, 2006). This distinction permitted the assessment of the effects of a direct mechanical insult with and without local cell death on astrogliotic induction in a 3-D environment.…”

Section: Discussionmentioning

confidence: 99%

“…Neuronal-astrocytic co-cultures were mechanically loaded using the 3-D CSD, a custombuilt electromechanical device capable of reproducibly imparting high strain rate shear deformation to 3-D cell-containing matrices (LaPlaca et al, 2005). At the time of injury, cultures were removed from the incubator and mounted within the 3-D CSD.…”

Section: Mechanical Loading Using the 3-d Cell Shearing Devicementioning

confidence: 99%

“…Accordingly, we hypothesized that strain rate influences cellular responses following mechanical injury, resulting in varying degrees of cell death and astrogliotic alterations. To test this hypothesis, we utilized a well-characterized in vitro injury model in which shear deformation was imparted to thick (>500 μm) three-dimensional (3-D) neuronal-astrocytic co-cultures at a prescribed strain rate and magnitude (LaPlaca et al, 2005;Cullen and LaPlaca, 2006). This in vitro injury model reduces some of the complexity associated with in vivo experiments, thus minimizing potentially confounding variables and facilitating more direct investigation of the effects of mechanical insult severity.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

2007

Self Cite

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: 85%

Section: Discussionmentioning

confidence: 99%

Section: Mechanical Loading Using the 3-d Cell Shearing Devicementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…Laplaca et al cultured cells in a gel and generated 3D deformation of the cells by producing a shear deformation of the gel (strain < 50%, strain rate < 30/s). Neuronal cells showed a lower tolerance to this strain than the glial cells (LaPlaca et al, 2005;Cullen et al, 2007).Tamura et al analyzed the difference in strain caused by a tensile test between porcine brain tissue and nerve fiber in the white matter, and reported that the maximum neural fiber strain was ~25% of the level in the surrounding tissue (Tamura et al, 2006). Nakayama et al showed morphological changes of axons and the progress of this damage over time caused by one-dimensional, horizontal oscillations of nerve cells (Nakayama et al, 2001).…”

Section: The Mechanism Of Daimentioning

confidence: 99%

Study on the Mechanism of Traumatic Brain Injury

Zhang¹,

Aomura²,

Nakadate³

et al. 2012

Applied Biological Engineering - Principles and Practice

View full text Add to dashboard Cite

Engineered Axonal Tracts as “Living Electrodes” for Synaptic‐Based Modulation of Neural Circuitry

Serruya

Harris

Adewole

et al. 2017

Adv Funct Materials

View full text Add to dashboard Cite

Brain-computer interface and neuromodulation strategies relying on penetrating non-organic electrodes/optrodes are limited by an inflammatory foreign body response that ultimately diminishes performance. A novel "biohybrid" strategy is advanced, whereby living neurons, biomaterials, and microelectrode/optical technology are used together to provide a biologicallybased vehicle to probe and modulate nervous-system activity. Microtissue engineering techniques are employed to create axon-based "living electrodes", which are columnar microstructures comprised of neuronal population(s) projecting long axonal tracts within the lumen of a hydrogel designed to chaperone delivery into the brain. Upon microinjection, the axonal segment penetrates to prescribed depth for synaptic integration with local host neurons, with the perikaryal segment remaining externalized below conforming electrical-optical arrays. In this paradigm, only the biological component ultimately remains in the brain, potentially attenuating a chronic foreign-body This article is protected by copyright. All rights reserved. 4 response. Axon-based living electrodes are constructed using multiple neuronal subtypes, each with differential capacity to stimulate, inhibit, and/or modulate neural circuitry based on specificity uniquely afforded by synaptic integration, yet ultimately computer controlled by optical/electrical components on the brain surface. Current efforts are assessing the efficacy of this biohybrid interface for targeted, synaptic-based neuromodulation, and the specificity, spatial density and longterm fidelity versus conventional microelectronic or optical substrates alone.

show abstract

High rate shear strain of three-dimensional neural cell cultures: a new in vitro traumatic brain injury model

Cited by 194 publications

References 40 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

Study on the Mechanism of Traumatic Brain Injury

Engineered Axonal Tracts as “Living Electrodes” for Synaptic‐Based Modulation of Neural Circuitry

Contact Info

Product

Resources

About