The effect of explosive blast loading on human neuroblastoma cells

Zander, Nicole E.; Piehler, Thuvan; Banton, Rohan; Boggs, Mary

doi:10.1016/j.ab.2016.03.009

Cited by 12 publications

(7 citation statements)

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“…The pressure profile generated from such devices also may not match the specific profile produced by military explosives (see Chen and Constantini, 2013). Accordingly, precise RDX assemblies and their localized detonations were a key addition to the new blast paradigm, and they were shown to alter membrane permeability and induce axonal beading in PC12 cells and human neuroblastoma cells (Zander et al, 2015, 2016). While these two previous reports utilized dissociated cells, the current study made use of hippocampal slice cultures.…”

Section: Discussionmentioning

confidence: 99%

Blast waves from detonated military explosive reduce GluR1 and synaptophysin levels in hippocampal slice cultures

Smith

Piehler

Benjamin

et al. 2016

Experimental Neurology

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Explosives create shockwaves that cause blast-induced neurotrauma, one of the most common types of traumatic brain injury (TBI) linked to military service. Blast-induced TBIs are often associated with reduced cognitive and behavioral functions due to a variety of factors. To study the direct effects of military explosive blasts on brain tissue, we removed systemic factors by utilizing rat hippocampal slice cultures. The long-term slice cultures were briefly sealed air-tight in serum-free medium, lowered into a 37 °C water-filled tank, and small 1.7-gram assemblies of cyclotrimethylene trinitramine (RDX) were detonated 15 cm outside the tank, creating a distinct shockwave recorded at the culture plate position. Compared to control mock-treated groups of slices that received equal submerge time, 1–3 blast impacts caused a dose-dependent reduction in the AMPA receptor subunit GluR1. While only a small reduction was found in hippocampal slices exposed to a single RDX blast and harvested 1–2 days later, slices that received two consecutive RDX blasts 4 min apart exhibited a 26–40% reduction in GluR1, and the receptor subunit was further reduced by 64–72% after three consecutive blasts. Such loss correlated with increased levels of HDAC2, a histone deacetylase implicated in stress-induced reduction of glutamatergic transmission. No evidence of synaptic marker recovery was found at 72 h post-blast. The presynaptic marker synaptophysin was found to have similar susceptibility as GluR1 to the multiple explosive detonations. In contrast to the synaptic protein reductions, actin levels were unchanged, spectrin breakdown was not detected, and Fluoro-Jade B staining found no indication of degenerating neurons in slices exposed to three RDX blasts, suggesting that small, sub-lethal explosives are capable of producing selective alterations to synaptic integrity. Together, these results indicate that blast waves from military explosive cause signs of synaptic compromise without producing severe neurodegeneration, perhaps explaining the cognitive and behavioral changes in those blast-induced TBI sufferers that have no detectable neuropathology.

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Section: Discussionmentioning

confidence: 99%

Blast waves from detonated military explosive reduce GluR1 and synaptophysin levels in hippocampal slice cultures

Smith

Piehler

Benjamin

et al. 2016

Experimental Neurology

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“…In brief, cell culture well plates were mounted, secured, and immersed horizontally in a 10‐gallon poly(methyl methacrylate) aquarium containing water heated to 37°C (Fig. ; a cartoon schematic of the setup has been provided by Zander et al, ). The charge standoff distance was adjusted to generate ∼10–14 psi pressure measured 2 in.…”

Section: Methodsmentioning

confidence: 99%

Effects of repetitive low‐pressure explosive blast on primary neurons and mixed cultures

Zander

Piehler

Banton

et al. 2016

J of Neuroscience Research

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Repetitive mild traumatic brain injury represents a considerable health concern, particularly for athletes and military personnel. For blast-induced brain injury, threshold shock-impulse levels required to induce such injuries and cumulative effects with single and/or multiple exposures are not well characterized. Currently, there is no established in vitro experimental model with blast pressure waves generated by live explosives. This study presents results of primary neurons and mixed cultures subjected to our unique in vitro indoor experimental platform that uses real military explosive charges to probe the effects of primary explosive blast at the cellular level. The effects of the blast on membrane permeability, generation of reactive oxygen species (ROS), uptake of sodium ions, intracellular calcium, and release of glutamate were probed 2 and 24 hr postblast. Significant changes in membrane permeability and sodium uptake among the sham, single-blast-injured, and triple-blast-injured samples were observed. A significant increase in ROS and glutamate release was observed for the triple-blast-injured samples compared with the sham. Changes in intracellular calcium were not significant. These results suggest that blast exposure disrupts the integrity of the plasma membrane, leading to the upset of ion homeostasis, formation of ROS, and glutamate release. Published 2016. †This article is a U.S. Government work and is in the public domain in the USA.

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“…These mechanisms are varied and can include an increase in phosphorylated tau protein and beta amyloid deposition, inflammation, oxidative stress, mitochondrial dysfunction, and activation of microglia 62. The activation of these pathways can lead to cell death in experimental models through various molecular mechanisms that depend on the blast intensity and resultant tissue loading 63–65. The response to blast exposure may also depend on the physical properties of the tissue66–69 and physical properties surrounding the tissue, such as the shape of the face and the use of eye armor in the case of ocular injury 70.…”

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confidence: 99%

Blast Preconditioning Protects Retinal Ganglion Cells and Reveals Targets for Prevention of Neurodegeneration Following Blast-Mediated Traumatic Brian Injury

Harper

Woll

Evans

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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The effect of explosive blast loading on human neuroblastoma cells

Cited by 12 publications

References 11 publications

Blast waves from detonated military explosive reduce GluR1 and synaptophysin levels in hippocampal slice cultures

Blast waves from detonated military explosive reduce GluR1 and synaptophysin levels in hippocampal slice cultures

Effects of repetitive low‐pressure explosive blast on primary neurons and mixed cultures

Blast Preconditioning Protects Retinal Ganglion Cells and Reveals Targets for Prevention of Neurodegeneration Following Blast-Mediated Traumatic Brian Injury

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