Blast induced neurotrauma causes overpressure dependent changes to the DNA methylation equilibrium

Bailey, Zachary S.; Grinter, Michael B.; Campos, Diego; VandeVord, Pamela J.

doi:10.1016/j.neulet.2015.07.035

Cited by 25 publications

(19 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An in-depth study into the transcriptional expression patterns of the enzymes responsible for controlling DNA methylation and demethylation has shown that different levels of blast injury may trigger distinct pathways in specific brain regions, and produce different cellular responses to the injury [4]. Expression changes were observed in enzymes controlling DNA methylation, such as DNMTs, TETs and thymine-DNA glycosylase (TDG).…”

Section: Neuroepigeneticsmentioning

confidence: 99%

“…Expression changes were observed in enzymes controlling DNA methylation, such as DNMTs, TETs and thymine-DNA glycosylase (TDG). The hippocampus was more vulnerable to enzyme expression changes than the prefrontal cortex, which correlated with aberrant DNA methylation [4]. A significant negative correlation was found between global DNA methylation and the magnitude of blast overpressure exposure.…”

Section: Neuroepigeneticsmentioning

confidence: 99%

“…A significant negative correlation was found between global DNA methylation and the magnitude of blast overpressure exposure. It is thought that altered DNA methylation patterns may offer insight into the characteristic outcomes associated with the injury pathology including inflammation, oxidative stress and apoptosis [4]. As such, these enzymes will be important targets for future therapeutic intervention strategies.…”

Section: Neuroepigeneticsmentioning

confidence: 99%

See 2 more Smart Citations

Epigenetic changes following traumatic brain injury and their implications for outcome, recovery and therapy

Wong

Langley

2016

Neuroscience Letters

View full text Add to dashboard Cite

Traumatic brain injury (TBI) contributes to nearly a third of all injury-related deaths in the United States. For survivors of TBI, depending on severity, patients can be left with devastating neurological disabilities that include impaired cognition or memory, movement, sensation, or emotional function. Despite the efforts to identify novel therapeutics, the only strategy to combat TBI is risk reduction (helmets, seatbelts, removal of fall hazards, etc.). Enormous heterogeneity exists within TBI, and it depends on the severity, the location, and whether the injury was focal or diffuse. Evidence from recent studies support the involvement of epigenetic mechanisms such as DNA methylation, chromatin post-translational modification, and miRNA regulation of gene expression in the post-injured brain. In this review, we discuss studies that have assessed epigenetic changes and mechanisms following TBI, how epigenetic changes might not only be limited to the nucleus but also impact the mitochondria, and the implications of these changes with regard to TBI recovery.

show abstract

Section: Neuroepigeneticsmentioning

confidence: 99%

Section: Neuroepigeneticsmentioning

confidence: 99%

Section: Neuroepigeneticsmentioning

confidence: 99%

See 1 more Smart Citation

Epigenetic changes following traumatic brain injury and their implications for outcome, recovery and therapy

Wong

Langley

2016

Neuroscience Letters

View full text Add to dashboard Cite

show abstract

“…Experimental traumatic brain injury (TBI) modifies the distribution and expression of Dnmt1, as well as DNA methylation at both the cellular and organ levels [72,73]. A recent study suggests that DNA hypomethylation and hypermethylation changes occur in both neurons and glia.…”

Section: Epigenetic Modifications Following Central Nervous System Inmentioning

confidence: 99%

“…These changes appear to be dependent on specific DNA regions, and thus the gene regions with which the methylation patterns are associated. In specific neuronal populations, epigenetic changes in Dnmt expression and DNA methylation as well as HDAC expression have been documented, which suggest subpopulation-specific neuronal responses to blast-type brain injury [72,74]. Blast-injury, among other forms of experimental TBI, causes mild forms of brain damage and diffuse axonal injury.…”

Section: Epigenetic Modifications Following Central Nervous System Inmentioning

confidence: 99%

Transcriptional and Epigenetic Regulation in Injury-Mediated Neuronal Dendritic Plasticity

Wang

et al. 2016

Neurosci. Bull.

View full text Add to dashboard Cite

Injury to the nervous system induces localized damage in neural structures and neuronal death through the primary insult, as well as delayed atrophy and impaired plasticity of the delicate dendritic fields necessary for interneuronal communication. Excitotoxicity and other secondary biochemical events contribute to morphological changes in neurons following injury. Evidence suggests that various transcription factors are involved in the dendritic response to injury and potential therapies. Transcription factors play critical roles in the intracellular regulation of neuronal morphological plasticity and dendritic growth and patterning. Mounting evidence supports a crucial role for epigenetic modifications via histone deacetylases, histone acetyltransferases, and DNA methyltransferases that modify gene expression in neuronal injury and repair processes. Gene regulation through epigenetic modification is of great interest in neurotrauma research, and an early picture is beginning to emerge concerning how injury triggers intracellular events that modulate such responses. This review provides an overview of injury-mediated influences on transcriptional regulation through epigenetic modification, the intracellular processes involved in the morphological consequences of such changes, and potential approaches to the therapeutic manipulation of neuronal epigenetics for regulating gene expression to facilitate growth and signaling through dendritic arborization following injury.

show abstract

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

Zander

Piehler

Banton

et al. 2016

J of Neuroscience Research

View full text Add to dashboard Cite

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.

show abstract

Blast induced neurotrauma causes overpressure dependent changes to the DNA methylation equilibrium

Cited by 25 publications

References 33 publications

Epigenetic changes following traumatic brain injury and their implications for outcome, recovery and therapy

Epigenetic changes following traumatic brain injury and their implications for outcome, recovery and therapy

Transcriptional and Epigenetic Regulation in Injury-Mediated Neuronal Dendritic Plasticity

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

Contact Info

Product

Resources

About