Blood-Brain Barrier Dysfunction after Primary Blast Injury<i>in vitro</i>

Hue, Christopher Donald; Cao, Siqi; Haider, Syed Farrukh; Vo, Kiet V.; Effgen, Gwen Brink; Vogel, Edward W.; Panzer, Matthew B.; Bass, Cameron R.; Meaney, David F.; Morrison, Barclay

doi:10.1089/neu.2012.2773

Cited by 59 publications

(99 citation statements)

References 86 publications

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“…This difference could be because bEnd.3 cells are less differentiated than brain-derived microvessel endothelial cells, and which form barriers with lower TEER values than primary brain endothelial cultures used in this report [27]. Nonetheless, our findings in BMECs and in vitro blast studies using bEnd.3 cells [43,44], collectively demonstrate that blast exposure disturbs expression of proteins critical for maintaining BBB integrity.…”

Section: Transverse Riemann Solversmentioning

confidence: 67%

“…Previous work using the continuous cell line, bEnd.3 showed that blast causes a loss of ZO1 and claudin-5 [43,44]. This difference could be because bEnd.3 cells are less differentiated than brain-derived microvessel endothelial cells, and which form barriers with lower TEER values than primary brain endothelial cultures used in this report [27].…”

Section: Transverse Riemann Solversmentioning

confidence: 72%

“…This suggests that the injury mechanisms might occur at very small length scales, even at the scale of a single cell. Several hypothesis have been proposed: the disruption of BBB integrity [88,43,76]; cerebral vasospasm mechanotransduced by the blast wave [3]; impairment of axonal functionality [57,58]; shock wave excitation of phonons that decay into lower frequency oscillations [49] and the formation of cavitating bubbles [71,67,66,80,109,74,37], among others.…”

mentioning

confidence: 99%

“…In this paper, we study blast-induced BBB using differentiated brain-derived microvessel endothelial cells, considered the biologically most relevant in vitro approach for investigating BBB function [43,44] (see Appendix for further discussion). Understanding such experiments is important since they isolate one possible cause of TBIresults show that blast functionally disturbs the BBB endothelial cell tight junction protein expression patterns.…”

mentioning

confidence: 99%

“…The cylindrical transwell chamber was then completely filled with tissue culture media, sealed against leaks, placed inside a shock tube, and exposed to the blast, as shown in Figure 1.1(b). Blast exposure has been shown to impair tight junction integrity under in vitro conditions, as well [43].…”

mentioning

confidence: 99%

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Computational and In Vitro Studies of Blast-Induced Blood-Brain Barrier Disruption

Razo

Morofuji

Meabon

et al. 2016

SIAM J. Sci. Comput.

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Abstract. There is growing concern that blast-exposed individuals are at risk of developing neurological disorders later in life. Therefore, it is important to understand the dynamic properties of blast forces on brain cells, including the endothelial cells that maintain the blood-brain barrier (BBB), which regulates the passage of nutrients into the brain and protects it from toxins in the blood. To better understand the effect of shock waves on the BBB we have investigated an in vitro model in which BBB endothelial cells are grown in transwell vessels and exposed in a shock tube, confirming that BBB integrity is directly related to shock wave intensity. It is difficult to directly measure the forces acting on these cells in the transwell container during the experiments, and so a computational tool has been developed and presented in this paper.Two-dimensional axisymmetric Euler equations with the Tammann equation of state were used to model the transwell materials, and a high-resolution finite volume method based on Riemann solvers and the Clawpack software was used to solve these equations in a mixed Eulerian/Lagrangian frame. Results indicated that the geometry of the transwell plays a significant role in the observed pressure time series in these experiments. We also found that pressures can fall below vapor pressure due to the interaction of reflecting and diffracting shock waves, suggesting that cavitation bubbles could be a damage mechanism. Computations that include a simulated hydrophone inserted in the transwell suggest that the instrument itself could significantly alter blast wave properties. These findings illustrate the need for further computational modeling studies aimed at understanding possible blastinduced BBB damage.

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Section: Transverse Riemann Solversmentioning

confidence: 67%

Section: Transverse Riemann Solversmentioning

confidence: 72%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Computational and In Vitro Studies of Blast-Induced Blood-Brain Barrier Disruption

Razo

Morofuji

Meabon

et al. 2016

SIAM J. Sci. Comput.

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In vitro studies of primary explosive blast loading on neurons

Zander

Piehler

Boggs

et al. 2015

J of Neuroscience Research

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In a military setting, traumatic brain injury (TBI) is frequently caused by blast waves that can trigger a series of neuronal biochemical changes. Although many animal models have been used to study the effects of primary blast waves, elucidating the mechanisms of damage in a whole-animal model is extremely complex. In vitro models of primary blast, which allow for the deconvolution of mechanisms, are relatively scarce. It is largely unknown how structural damage at the cellular level impacts the functional activity at variable time scales after the TBI event. A novel in vitro system was developed to probe the effects of explosive blast (ranging from ∼25 to 40 psi) on dissociated neurons. PC12 neurons were cultured on laminin-coated substrates, submerged underwater, and subjected to single and multiple blasts in a controlled environment. Changes in cell membrane permeability, viability, and cell morphology were evaluated. Significant increases in axonal beading were observed in the injured cells. In addition, although cell death was minimal after a single insult, cell viability decreased significantly following repeated blast exposure.

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