Astrocyte Viability and Functionality in Spatially Confined Microcavitation Zone

Chen, Bin; Tjahja, Jessica; Malla, Sameep; Liebman, Caleb; Cho, Michael

doi:10.1021/acsami.8b21410

Cited by 12 publications

(10 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We coined the term microcavitation to describe the process and was able to quantitatively study the interaction between brain endothelial cells and the collapse of highly pressurized microbubbles. The collapse of microbubbles (~55 kPa; ~10 s interaction time) was observed to detach cells from the substrate and created a region that is devoid of cells 35 . The area of cell detachment has been referred to as a crater.…”

Section: Discussionmentioning

confidence: 99%

Modulation of in vitro Brain Endothelium by Mechanical Trauma: Structural and Functional Restoration by Poloxamer 188

Inyang

Abhyankar

Chen

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Brain injuries caused by an explosive blast or blunt force is typically presumed to associate with mechanical trauma to the brain tissue. Recent findings from our laboratory suggest that shockwaves produced by a blast can generate micron-sized bubbles in the tissue. the collapse of microbubbles (i.e., microcavitation) may induce a mechanical trauma and compromise the integrity of the blood-brain endothelium (BBE). To test our hypothesis, we engineered a BBE model to determine the effect of microbubbles on the structural and functional changes in the BBe. Using monolayers of mouse primary brain microvascular endothelial cells, the permeability coefficient was measured following simulated blast-induced microcavitation. this event down-regulated the expression of tight junction markers, disorganized the cell-cell junction, and increased permeability. Since poloxamers have been shown to rescue damaged cells, the cells were treated with the FDA-approved poloxamer 188 (P188). The results indicate P188 recovered the permeability, restored the tight junctions, and suppressed the expressions of matrix metalloproteinases. the biomimetic interface we developed appears to provide a systematic approach to replicate the structure and function of BBe, determine its alteration in response to traumatic brain injury, and test potential therapeutic treatments to repair the damaged brain endothelium. Traumatic brain injury (TBI) is one of the major causes of emergency visits and hospitalization. In 2010, the Centers for Disease Control reported about 2.5 million emergency department visits, hospitalizations, and deaths here in the United States alone 1. TBIs are also caused by an explosive blast or blunt force to the head especially among those who serve in the U.S. military 2-4. The trauma can lead to endothelial cell detachment, tight junction disruption, and altered blood-brain barrier (BBB) permeability 5,6. One of the unique features of BBB is the regulation of biotransport through a monolayer of brain endothelial cells (BECs). BECs are highly regulated in their structure and function by the tight junction complex that is composed of, among many molecules, zonula occludens (ZO-1) and the occludins family 7,8. Only particles with a molecular mass of less than 500 Daltons can cross the BBB efficiently 9. However, the structural integrity of the BBB can be mechanically and biochemically compromised 10-13 , allowing harmful substances to extravasate into the brain. The leaky brain endothelium, in turn, may lead to secondary brain injury 14-16. Several sophisticated TBI models of explosive blast or blunt force have been studied. However, the potential mechanisms connecting shock wave exposure to the head and to TBI are still not well understood 17. One of the mechanical traumas that have been investigated in our laboratory is the formation of micron-size bubbles in response to shock wave and subsequent collapse of such microbubbles, referred to as microcavitation 18. The collapse of highly pressurized microbubbles is thought to prod...

show abstract

Section: Discussionmentioning

confidence: 99%

Modulation of in vitro Brain Endothelium by Mechanical Trauma: Structural and Functional Restoration by Poloxamer 188

Inyang

Abhyankar

Chen

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Next, the E-selectin expression was then examined in response to a mechanical trauma (microcavitation). One of the characteristics of this particular mechanical injury was shown to create a lesion in which the cells are detached following the collapse of highly pressurized microbubbles. ,, This mechanically induced event is explicitly demonstrated by the formation of approximately a circular area (∼100 μm diameter; Figure L) in which endothelial cells are detached. There are two observations to note.…”

Section: Resultsmentioning

confidence: 99%

Engineering Delivery of Nonbiologics Using Poly(lactic-co-glycolic acid) Nanoparticles for Repair of Disrupted Brain Endothelium

et al. 2020

Self Cite

View full text Add to dashboard Cite

Traumatic brain injury (TBI) is known to alter the structure and function of the blood–brain barrier (BBB). Blunt force or explosive blast impacting the brain can cause neurological sequelae through the mechanisms that remain yet to be fully elucidated. For example, shockwaves propagating through the brain have been shown to create a mechanical trauma that may disrupt the BBB. Indeed, using tissue engineering approaches, the shockwave-induced mechanical injury has been shown to modulate the organization and permeability of the endothelium tight junctions. Because an injury to the brain endothelium typically induces a high expression of E-selectin, we postulated that upregulation of this protein after an injury can be exploited for diagnosis and potential therapy through targeted nanodelivery to the injured brain endothelium. To test this hypothesis, we engineered poly(lactic-co-glycolic acid) (PLGA) nanoparticles to encapsulate therapeutic nonbiologics and decorated them with ligands to specifically target the E-selectin. A high level of the conjugated nanoparticles was found inside the injured cells. Repair of the injury site was then quantitatively measured and analyzed. To summarize, exploiting the tunable properties of PLGA, a targeted drug delivery strategy has been developed and validated, which combines the specificity of ligand/receptor interaction with therapeutic reagents. Such a strategy could be used to provide a potential theragnostic approach for the treatment of modulated brain endothelium associated with TBI.

show abstract

“…One possible explanation for this significant difference in cell response before/after impact is that the amplitude of cavitation-induced pressure may be much larger than acceleration-induced pressure. However, a recent study reported that pressure associated with bubble collapse of thermally induced cavitation is about 56 kPa 19 , which is considerably smaller than the critical pressure, using a pressure sensitive film. Another possible mechanism is that cavitation-induced pressure, i.e., a rate of the pressure change in time, is much faster than acceleration-induced pressure and, as a result, viscoelastic response of cells, i.e., cell damage response, at different loading rates could be significantly different 28 .…”

Section: The Main Injury Mechanism: Cavitationmentioning

confidence: 91%

“…Dynamic cavitation in the brain is increasingly considered a potential damage mechanism for traumatic brain injury [16][17][18][19][20] . In this regard, one notable advance is in the characterization of cavitation properties for soft biomaterials under an impulsive force [21][22][23] .…”

Section: Mechanisms Of Cell Damage Due To Mechanical Impact: An In VImentioning

confidence: 99%

Mechanisms of cell damage due to mechanical impact: an in vitro investigation

Kang

Robitaille

Merrill

et al. 2020

Sci Rep

View full text Add to dashboard Cite

The dynamic response of cells when subjected to mechanical impact has become increasingly relevant for accurate assessment of potential blunt injuries and elucidating underlying injury mechanisms. When exposed to mechanical impact, a biological system such as the human skin, brain, or liver is rapidly accelerated, which could result in blunt injuries. For this reason, an acceleration of greater than > 150 g is the most commonly used criteria for head injury. To understand the main mechanism(s) of blunt injury under such extreme dynamic threats, we have developed an innovative experimental method that applies a well-characterized and -controlled mechanical impact to live cells cultured in a custom-built in vitro setup compatible with live cell microscopy. Our studies using fibroblast cells as a model indicate that input acceleration ($${a}_{in}$$ain) alone, even when it is much greater than the typical injury criteria, e.g., $${a}_{in}>1{,}000$$ain>1,000 g, does not result in cell damage. On the contrary, we have observed a material-dependent critical pressure value above which a sudden decrease in cell population and cell membrane damage have been observed. We have unambiguously shown that (1) this critical pressure is associated with the onset of cavitation bubbles in a cell culture chamber and (2) the dynamics of cavitation bubbles in the chamber induces localized compressive/tensile pressure cycles, with an amplitude that is considerably greater than the acceleration-induced pressure, to cells. More importantly, the rate of pressure change with time for cavitation-induced pressure is significantly faster (more than ten times) than acceleration-induced pressure. Our in vitro study on the dynamic response of biological systems due to mechanical impact is a crucial step towards understanding potential mechanism(s) of blunt injury and implementing novel therapeutic strategies post-trauma.

show abstract

Astrocyte Viability and Functionality in Spatially Confined Microcavitation Zone

Cited by 12 publications

References 51 publications

Modulation of in vitro Brain Endothelium by Mechanical Trauma: Structural and Functional Restoration by Poloxamer 188

Modulation of in vitro Brain Endothelium by Mechanical Trauma: Structural and Functional Restoration by Poloxamer 188

Engineering Delivery of Nonbiologics Using Poly(lactic-co-glycolic acid) Nanoparticles for Repair of Disrupted Brain Endothelium

Mechanisms of cell damage due to mechanical impact: an in vitro investigation

Contact Info

Product

Resources

About