Dataset Information

Comprehensive Characterization of Cerebrovascular Dysfunction in Blast Traumatic Brain Injury Using Photoacoustic Microscopy.

ABSTRACT: Blast traumatic brain injury (bTBI) is a leading contributor to combat-related injuries and death. Although substantial emphasis has been placed on blast-induced neuronal and axonal injuries, co-existing dysfunctions in the cerebral vasculature, particularly the microvasculature, remain poorly understood. Here, we studied blast-induced cerebrovascular dysfunctions in a rat model of bTBI (blast overpressure: 187.8?±?18.3?kPa). Using photoacoustic microscopy (PAM), we quantified changes in cerebral hemodynamics and metabolism-including blood perfusion, oxygenation, flow, oxygen extraction fraction, and the metabolic rate of oxygen-4?h post-injury. Moreover, we assessed the effect of blast exposure on cerebrovascular reactivity (CVR) to vasodilatory stimulation. With vessel segmentation, we extracted these changes at the single-vessel level, revealing their dependence on vessel type (i.e., artery vs. vein) and diameter. We found that bTBI at this pressure level did not induce pronounced baseline changes in cerebrovascular diameter, blood perfusion, oxygenation, flow, oxygen extraction, and metabolism, except for a slight sO₂ increase in small veins (<45??m) and blood flow increase in large veins (?45??m). In contrast, this blast exposure almost abolished CVR, including arterial dilation, flow upregulation, and venous sO₂ increase. This study is the most comprehensive assessment of cerebrovascular structure and physiology in response to blast exposure to date. The observed impairment in CVR can potentially cause cognitive decline due to the mismatch between cognitive metabolic demands and vessel's ability to dynamically respond to meet the demands. Also, the impaired CVR can lead to increased vulnerability of the brain to metabolic insults, including hypoxia and ischemia.

SUBMITTER: Cao R

PROVIDER: S-EPMC6532277 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Comprehensive Characterization of Cerebrovascular Dysfunction in Blast Traumatic Brain Injury Using Photoacoustic Microscopy.

Cao Rui R Zhang Chenchu C Mitkin Vladimir V VV Lankford Miles F MF Li Jun J Zuo Zhiyi Z Meyer Craig H CH Goyne Christopher P CP Ahlers Stephen T ST Stone James R JR Hu Song S

Journal of neurotrauma 20190125 10

Blast traumatic brain injury (bTBI) is a leading contributor to combat-related injuries and death. Although substantial emphasis has been placed on blast-induced neuronal and axonal injuries, co-existing dysfunctions in the cerebral vasculature, particularly the microvasculature, remain poorly understood. Here, we studied blast-induced cerebrovascular dysfunctions in a rat model of bTBI (blast overpressure: 187.8 ± 18.3 kPa). Using photoacoustic microscopy (PAM), we quantified changes in cerebra ...[more]

PMID: 30501547

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Project description:Long-term molecular changes in the brain resulting from blast exposure may be mediated by epigenetic changes, such as deoxyribonucleic acid (DNA) methylation, that regulate gene expression. Aberrant regulation of gene expression is associated with behavioral abnormalities, where DNA methylation bridges environmental signals to sustained changes in gene expression. We assessed DNA methylation changes in the brains of rats exposed to three 74.5 kPa blast overpressure events, conditions that have been associated with long-term anxiogenic manifestations weeks or months following the initial exposures. Rat frontal cortex eight months post-exposure was used for cell sorting of whole brain tissue into neurons and glia. We interrogated DNA methylation profiles in these cells using Expanded Reduced Representation Bisulfite Sequencing. We obtained data for millions of cytosines, showing distinct methylation profiles for neurons and glia and an increase in global methylation in neuronal versus glial cells (p<10(-7)). We detected DNA methylation perturbations in blast overpressure-exposed animals, compared with sham blast controls, within 458 and 379 genes in neurons and glia, respectively. Differentially methylated neuronal genes showed enrichment in cell death and survival and nervous system development and function, including genes involved in transforming growth factor β and nitric oxide signaling. Functional validation via gene expression analysis of 30 differentially methylated neuronal and glial genes showed a 1.2 fold change in gene expression of the serotonin N-acetyltransferase gene (Aanat) in blast animals (p<0.05). These data provide the first genome-based evidence for changes in DNA methylation induced in response to multiple blast overpressure exposures. In particular, increased methylation and decreased gene expression were observed in the Aanat gene, which is involved in converting serotonin to the circadian hormone melatonin and is implicated in sleep disturbance and depression associated with traumatic brain injury.

Dataset Information

Comprehensive Characterization of Cerebrovascular Dysfunction in Blast Traumatic Brain Injury Using Photoacoustic Microscopy.

Publications

Comprehensive Characterization of Cerebrovascular Dysfunction in Blast Traumatic Brain Injury Using Photoacoustic Microscopy.

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