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Blast induced neurotrauma

Saranya Canchi, Malisa Sarntinoranont, Yu Hong, Jeremy J Flint, Ghatu Subhash, Michael A King
Exposure to explosive blasts can produce functional debilitation in the absence of brain pathology detectable at the scale of current diagnostic imaging. Transient (ms) overpressure components of the primary blast wave are considered to be potentially damaging to the brain. Astrocytes participate in neuronal metabolic maintenance, blood-brain barrier, regulation of homeostatic environment, and tissue remodeling. Damage to astrocytes via direct physical forces has the potential to disrupt local and global functioning of neuronal tissue...
2017: PloS One
Namas Chandra, Aravind Sundaramurthy, Raj K Gupta
Blast-induced neurotrauma has affected more than 300,000 service members. It is important to understand the effect of single and repeated shock-blast wave exposures on the neuropsychological behavior of soldiers, to offer them better protection, diagnostics, and treatment. Preclinical animal models and helmet design studies on human surrogate models have relied on the use of compression gas-driven shock tubes. Traditional shock tubes are so simple that if not carefully designed and operated, the test results can easily introduce detrimental artifacts clouding the conclusions...
March 2017: Military Medicine
Brandon P Lucke-Wold, Aric F Logsdon, Ryan C Turner, Jason D Huber, Charles L Rosen
Blast traumatic brain injury (bTBI) has been shown to contribute to progressive neurodegenerative disease. Recent evidence suggests that endoplasmic reticulum (ER) stress is a mechanistic link between acute neurotrauma and progressive tauopathy. We propose that ER stress contributes to extensive behavioral changes associated with a chronic traumatic encephalopathy (CTE)-like phenotype. Targeting ER stress is a promising option for the treatment of neurotrauma-related neurodegeneration, which warrants investigation...
February 27, 2017: Journal of Neurotrauma
Ke Feng, Liying Zhang, Xin Jin, Chaoyang Chen, Srinivasu Kallakuri, Tal Saif, John Cavanaugh, Albert King
Blast-induced traumatic brain injury (bTBI) is a signature wound of modern warfare. The current incomplete understanding of its injury mechanism impedes the development of strategies for effective protection of bTBI. Despite a considerable amount of experimental animal studies focused on the evaluation of brain neurotrauma caused by blast exposure, there is very limited knowledge on the biomechanical responses of the gyrenecephalic brain subjected to primary free-field blast waves imposed in vivo. This study aims to evaluate the external and internal mechanical responses of the brain against different levels of blast loading with Yucatan swine in free field...
2016: Frontiers in Neurology
Marquitta Smith, Thuvan Piehler, Richard Benjamin, Karen L Farizatto, Morgan C Pait, Michael F Almeida, Vladimir V Ghukasyan, Ben A Bahr
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...
October 5, 2016: Experimental Neurology
Zachary S Bailey, W Brad Hubbard, Pamela J VandeVord
Blast-induced neurotrauma (BINT) has increased in incidence over the past decades and can result in cognitive issues that have debilitating consequences. The exact primary and secondary mechanisms of injury have not been elucidated and appearance of cellular injury can vary based on many factors, such as blast overpressure magnitude and duration. Many methodologies to study blast neurotrauma have been employed, ranging from open-field explosives to experimental shock tubes for producing free-field blast waves...
2016: Methods in Molecular Biology
Zachary S Bailey, Michael B Grinter, Pamela J VandeVord
Blast induced neurotrauma (BINT) is a prevalent injury within military and civilian populations. The injury is characterized by persistent inflammation at the cellular level which manifests as a multitude of cognitive and functional impairments. Epigenetic regulation of transcription offers an important control mechanism for gene expression and cellular function which may underlie chronic inflammation and result in neurodegeneration. We hypothesize that altered histone acetylation patterns may be involved in blast induced inflammation and the chronic activation of glial cells...
2016: Frontiers in Molecular Neuroscience
Ying Wang, Yanling Wei, Samuel Oguntayo, Donna Wilder, Lawrence Tong, Yan Su, Irene Gist, Peethambaran Arun, Joseph B Long
Chemokines and their receptors are of great interest within the milieu of immune responses elicited in the central nervous system in response to trauma. Chemokine (C-C motif)) ligand 2 (CCL2), which is also known as monocyte chemotactic protein-1, has been implicated in the pathogenesis of traumatic brain injury (TBI), brain ischemia, Alzheimer's disease, and other neurodegenerative diseases. In this study, we investigated the time course of CCL2 accumulation in cerebrospinal fluid (CSF) after exposures to single and repeated blast overpressures of varied intensities along with the neuropathological changes and motor deficits resulting from these blast conditions...
February 15, 2017: Journal of Neurotrauma
Ya-Lei Ning, Nan Yang, Xing Chen, Zi-Ai Zhao, Xiu-Zhu Zhang, Xing-Yun Chen, Ping Li, Yan Zhao, Yuan-Guo Zhou
OBJECTIVE: To investigate the effects of three different ways of chronic caffeine administration on blast- induced memory dysfunction and to explore the underlying mechanisms. METHODS: Adult male C57BL/6 mice were used and randomly divided into five groups: control: without blast exposure, con-water: administrated with water continuously before and after blast-induced traumatic brain injury (bTBI), con-caffeine: administrated with caffeine continuously for 1 month before and after bTBI, pre-caffeine: chronically administrated with caffeine for 1 month before bTBI and withdrawal after bTBI, post-caffeine: chronically administrated with caffeine after bTBI...
2015: Chinese Journal of Traumatology, Zhonghua Chuang Shang za Zhi
Ryan C Turner, Brandon P Lucke-Wold, Aric F Logsdon, Matthew J Robson, Matthew L Dashnaw, Jason H Huang, Kelly E Smith, Jason D Huber, Charles L Rosen, Anthony L Petraglia
Chronic neurodegeneration following a history of neurotrauma is frequently associated with neuropsychiatric and cognitive symptoms. In order to enhance understanding about the underlying pathophysiology linking neurotrauma to neurodegeneration, a multi-model preclinical approach must be established to account for the different injury paradigms and pathophysiologic mechanisms. We investigated the development of tau pathology and behavioral changes using a multi-model and multi-institutional approach, comparing the preclinical results to tauopathy patterns seen in post-mortem human samples from athletes diagnosed with chronic traumatic encephalopathy (CTE)...
2015: Frontiers in Neurology
Venkata Siva Sai Sujith Sajja, W Brad Hubbard, Christina S Hall, Farhad Ghoddoussi, Matthew P Galloway, Pamela J VandeVord
Few preclinical studies have assessed the long-term neuropathology and behavioral deficits after sustaining blast-induced neurotrauma (BINT). Previous studies have shown extensive astrogliosis and cell death at acute stages (<7 days) but the temporal response at a chronic stage has yet to be ascertained. Here, we used behavioral assays, immmunohistochemistry and neurochemistry in limbic areas such as the amygdala (Amy), Hippocampus (Hipp), nucleus accumbens (Nac), and prefrontal cortex (PFC), to determine the long-term effects of a single blast exposure...
2015: Scientific Reports
Michael K Walls, Nicholas Race, Lingxing Zheng, Sasha M Vega-Alvarez, Glen Acosta, Jonghyuck Park, Riyi Shi
OBJECTIVE: Blast-induced neurotrauma (BINT), if not fatal, is nonetheless potentially crippling. It can produce a wide array of acute symptoms in moderate-to-severe exposures, but mild BINT (mBINT) is characterized by the distinct absence of acute clinical abnormalities. The lack of observable indications for mBINT is particularly alarming, as these injuries have been linked to severe long-term psychiatric and degenerative neurological dysfunction. Although the long-term sequelae of BINT are extensively documented, the underlying mechanisms of injury remain poorly understood, impeding the development of diagnostic and treatment strategies...
March 2016: Journal of Neurosurgery
Pamela J VandeVord, Venkata Siva Sai Sujith Sajja, Evon Ereifej, Amy Hermundstad, Shijie Mao, Timothy J Hadden
Endocrine disorders have been shown to be a consequence of blast traumatic brain injury in soldiers returning from military conflicts. Hormone deficiency and adrenocorticotropic hormone (ACTH) dysfunction can lead to symptoms such as fatigue, anxiety, irritability, insomnia, sexual dysfunction, and decreased quality of life. Given these changes following blast exposure, the current study focused on investigating chronic pathology within the hypothalamus following blast, in addition to systemic effects. An established rodent model of blast neurotrauma was used to induce mild blast-induced neurotrauma...
January 1, 2016: Journal of Neurotrauma
Zachary S Bailey, Michael B Grinter, Diego De La Torre Campos, Pamela J VandeVord
Traumatic brain injury (TBI) has a high prevalence in our society and often leads to morbidity and mortality. TBI also occurs frequently in a military setting where exposure to blast waves is common. Abnormal gene expression involved with oxidative stress, inflammation and neuronal apoptosis has been well documented following blast induced neurotrauma (BINT). Altered epigenetic transcriptional regulation through DNA methylation has been implicated in the pathology of the injury. Imbalance between DNA methylation and DNA demethylation may lead to altered methylation patterns and subsequent changes in gene transcription...
September 14, 2015: Neuroscience Letters
Yutaka Igarashi, Yoko Matsuda, Akira Fuse, Toshiyuki Ishiwata, Zenya Naito, Hiroyuki Yokota
Microwave technology has been widely used in numerous applications; however, excessive microwave exposure causes adverse effects, particularly in the brain. The present study aimed to evaluate the change in the number of neural cells and presence of apoptotic cells in rats for one month after exposure to excessive microwave radiation. The rats were exposed to 3.0 kW of microwaves for 0.1 sec and were sacrificed after 24 h (n=3), or 3 (n=3), 7 (n=3), 14 (n=3) or 28 days (n=4) of exposure. The neural cells were counted in the motor cortex and hippocampus [cornu ammonis 1 (CA1) and CA2] and the percentage of positive cells stained with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) were also measured, which detected apoptotic cell death in the choroid plexus in the lateral ventricle, motor cortex and hippocampus...
July 2015: Biomedical Reports
Nora Hlavac, Samuel Miller, Michael Grinter, Pamela VandeVord
Blast-induced neurotrauma (BINT) has become an increasingly significant concern in Veterans returning from warfare. Associated brain injury and cognitive deficits are difficult to diagnose as the nature of this injury is progressive. In order to better understand the mechanisms of BINT at the microscopic level, two- and three-dimensional models of astrocytes were studied. The 3-D model was developed using Matrigel® to embed the cells. Injury was induced by exposure to an overpressure of 20 psi (140 kPa) using a shock wave generator which simulates a free field blast profile...
2015: Biomedical Sciences Instrumentation
Zachary S Bailey, Venkata Silva Sai Sujith Sajja, W Brad Hubbard, Pamela J VandeVord
Blast induced neurotrauma (BINT) leads to widespread aberrant gene expression and molecular changes resulting in cognitive impairment. Enzymes such as HDAC2, HDAC6, SIRT1, DNMT1, DNMT3a and DNMT3b control histone acetylation and DNA methylation which play a major role in regulation of the transcriptome. Changes in the expression of these enzymes have been implicated in the pathology of traumatic brain injury (TBI) and Alzheimer’s disease (AD). We hypothesize that blast exposure will lead to changes in the expression of these enzymes which play a key role in injury progression and pathology...
2015: Biomedical Sciences Instrumentation
Shana A Nelson, Gerri A Wilson, Michelle Tucci, Hamed Benghuzzi
Recent reports in the literature show an increase in the risk of heart related events in patients treated with tricyclic antidepressants. There is also evidence that serotonin reuptake inhibitors (SSRIs) are negatively associated with heart failure. The objective of our study is to determine if cardiomyocytes in culture can be used as a tool to mimic clinical scenarios and to evaluate therapeutic concentrations of SSRIs (fluoxetine) and antidiabetic (troglitazone) medication. Cardiomyocytes were grown in a tissue culture environment and challenged with therapeutic concentrations of SSRIs alone or a combination of SSRIs and antidiabetic drugs...
2015: Biomedical Sciences Instrumentation
Mengdong Liu, Chi Zhang, Wenbo Liu, Peng Luo, Lei Zhang, Yuan Wang, Zhanjiang Wang, Zhou Fei
In current military conflicts and civilian terrorism, blast-induced traumatic brain injury (bTBI) is the primary cause of neurotrauma. However, the effects and mechanisms of bTBI are poorly understood. Although previous researchers have made significant contributions to establishing animal models for the simulation of bTBI, the precision and controllability of blast-induced injury in animal models must be improved. Therefore, we established a novel rat model to simulate blast-wave injury to the brain. To simulate different extents of bTBI injury, the animals were divided into moderate and severe injury groups...
2015: Frontiers in Cellular Neuroscience
Venkata Siva Sai Sujith Sajja, William B Hubbard, Pamela J VandeVord
Behavioral symptoms, such as anxiety, are widely reported after blast overpressure (BOP) exposure. Amygdalar vulnerability to increasing magnitudes of BOP has not been investigated, and single exposures to blast have been limited to acute (<72 h) assessment. Rats were exposed to a single low, moderate, or high BOP (10, 14, or 24 psi) with an advanced blast simulator to test the susceptibility of the amygdala. Anxiety-like behavior was observed in the low- and moderate-pressure groups when subjected to the light/dark box assessment 7 days after the blast but not in high-pressure group...
August 2015: Shock
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