Significant Head Accelerations Can Influence Immediate Neurological Impairments in a Murine Model of Blast-Induced Traumatic Brain Injury

2014 ◽  
Vol 136 (9) ◽  
Author(s):  
David M. Gullotti ◽  
Matthew Beamer ◽  
Matthew B. Panzer ◽  
Yung Chia Chen ◽  
Tapan P. Patel ◽  
...  

Although blast-induced traumatic brain injury (bTBI) is well recognized for its significance in the military population, the unique mechanisms of primary bTBI remain undefined. Animate models of primary bTBI are critical for determining these potentially unique mechanisms, but the biomechanical characteristics of many bTBI models are poorly understood. In this study, we examine some common shock tube configurations used to study blast-induced brain injury in the laboratory and define the optimal configuration to minimize the effect of torso overpressure and blast-induced head accelerations. Pressure transducers indicated that a customized animal holder successfully reduced peak torso overpressures to safe levels across all tested configurations. However, high speed video imaging acquired during the blast showed significant head accelerations occurred when animals were oriented perpendicular to the shock tube axis. These findings of complex head motions during blast are similar to previous reports [Goldstein et al., 2012, “Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model,” Sci. Transl. Med., 4(134), 134ra160; Sundaramurthy et al., 2012, “Blast-Induced Biomechanical Loading of the Rat: An Experimental and Anatomically Accurate Computational Blast Injury Model,” J. Neurotrauma, 29(13), pp. 2352–2364; Svetlov et al., 2010, “Morphologic and Biochemical Characterization of Brain Injury in a Model of Controlled Blast Overpressure Exposure,” J. Trauma, 69(4), pp. 795–804]. Under the same blast input conditions, minimizing head acceleration led to a corresponding elimination of righting time deficits. However, we could still achieve righting time deficits under minimal acceleration conditions by significantly increasing the peak blast overpressure. Together, these data show the importance of characterizing the effect of blast overpressure on head kinematics, with the goal of producing models focused on understanding the effects of blast overpressure on the brain without the complicating factor of superimposed head accelerations.

2019 ◽  
Vol 184 (Supplement_1) ◽  
pp. 265-272 ◽  
Author(s):  
Yansong Li ◽  
Zhangsheng Yang ◽  
Bin Liu ◽  
Celina Valdez ◽  
Mikulas Chavko ◽  
...  

AbstractObjectiveMild blast traumatic brain injury is commonly prevalent in modern combat casualty care and has been associated with the development of neurodegenerative conditions. However, whether primary lower level blast overpressure (LBOP) causes neurodegeneration and neuroinflammation remains largely unknown. The aim of our present study was to determine whether LBOP can cause neuroinflammation and neurodegeneration.MethodsAnesthetized rats were randomly assigned to LBOP group (70 kPa, n = 5) or sham group (without blast, n = 5). Histopathological and cytokine changes in brain tissue at 5 days post-injury were evaluated by hematoxylin-eosin staining and Bioplex assay, respectively.ResultsHistopathological assessment revealed neuronal degeneration and increased density of inflammatory cells in frontal and parietal cortex, hippocampus and thalamus in rats exposed to LBOP. LBOP exposure significantly elevated levels of pro-inflammatory cytokines (EPO, IL-1β, IL-6, IL-12, IL-18, and TNF-α) and chemokines (GRO and RANTES) as well as of an anti-inflammatory cytokine (IL-13) in the frontal cortex.ConclusionsThis study reveals a role of neuroinflammation in neurodegeneration after mild blast traumatic brain injury. Therapies that target this process might in warfighters might function either by attenuating the development of post-traumatic stress disorder, chronic traumatic encephalopathy and Alzheimer’s disease, or by slowing their progression.


Author(s):  
Nicole L. Ackermans ◽  
Merina Varghese ◽  
Bridget Wicinski ◽  
Joshua Torres ◽  
Rita De Gasperi ◽  
...  

Biomarkers ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 213-227 ◽  
Author(s):  
Matthew I. Hiskens ◽  
Anthony G. Schneiders ◽  
Mariana Angoa-Pérez ◽  
Rebecca K. Vella ◽  
Andrew S. Fenning

2019 ◽  
Vol 1723 ◽  
pp. 146400 ◽  
Author(s):  
Shalini Jaiswal ◽  
Andrew K. Knutsen ◽  
Colin M. Wilson ◽  
Amanda H. Fu ◽  
Laura B. Tucker ◽  
...  

2018 ◽  
Vol 89 (10) ◽  
pp. A42.1-A42
Author(s):  
Graham Neil SN ◽  
Jolly Amy E ◽  
Bourke Niall J ◽  
Scott Gregory ◽  
Cole James H ◽  
...  

BackgroundDementia rates are elevated after traumatic brain injury (TBI) and a subgroup develops chronic traumatic encephalopathy. Post-traumatic neurodegeneration can be measured by brain atrophy rates derived from neuroimaging, but it is unclear how atrophy relates to the initial pattern of injury.ObjectivesTo investigate the relationship between baseline TBI patterns and subsequent neurodegeneration measured by progressive brain atrophy.Methods55 patients after moderate-severe TBI (mean 3 years post-injury) and 20 controls underwent longitudinal MRI. Brain atrophy was quantified using the Jacobian determinant defined from volumetric T1 scans approximately one year apart. Diffuse axonal injury was measured using diffusion tensor imaging and focal injuries defined from T1 and FLAIR. Neuropsychological assessment was performed.ResultsAbnormal progressive brain atrophy was seen after TBI (~1.8%/year in white matter). This was accompanied by widespread reductions in fractional anisotropy, in keeping with the presence of diffuse axonal injury. There was a strong negative correlation between FA and brain atrophy, whereby areas of greater white matter damage showed greater atrophy over time.ConclusionsThe results show a strong relationship between the location of diffuse axonal injury and subsequent neurodegeneration. This suggests that TBI triggers progressive neurodegeneration through the long-lasting effects of diffuse axonal injury.


2019 ◽  
Vol 13 ◽  
pp. 117906951984993 ◽  
Author(s):  
Melissa Demock ◽  
Steven Kornguth

A mechanism that describes the progression of traumatic brain injury (TBI) to end-stage chronic traumatic encephalopathy (CTE) is offered in this article. This mechanism is based upon the observed increase in the concentration of both tau protein and of human leukocyte antigen (HLA) class I proteins; the HLA increase is expressed on the cell membrane of neural cells. These events follow the inflammatory responses caused by the repetitive TBI. Associated inflammatory changes include macrophage entry into the brain parenchyma from increased permeability of the blood-brain barrier (BBB) and microglial activation at the base of the sulci. The release of interferon gamma from the microglia and macrophages induces the marked increased expression of HLA class I proteins by the neural cells and subsequent redistribution of the tau proteins to the glial and neuronal surface. In those individuals with highly expressed HLA class I C, the high level of HLA binds tau protein electrostatically. The ionic region of HLA class I C (amino acid positions 50-90) binds to the oppositely charged ionic region of tau (amino acid positions 93-133). These interactions thereby shift the cellular localization of the tau and orient the tau spatially so that the cross-linking sites of tau (275-280 and 306-311) are aligned. This alignment facilitates the cross-linking of tau to form the intracellular and extracellular microfibrils of tau, the primary physiological characteristic of tauopathy. Following endocytosis of the membrane HLA/tau complex, these microfibrils accumulate and produce a tau-storage-like disease. Therefore, tauopathy is the secondary collateral process of brain injury, resulting from the substantial increase in tau and HLA expression on neural cells. This proposed mechanism suggests several potential targets for mitigating the clinical progression of TBI to CTE.


2010 ◽  
Vol 69 (4) ◽  
pp. 795-804 ◽  
Author(s):  
Stanislav I. Svetlov ◽  
Victor Prima ◽  
Daniel R. Kirk ◽  
Hector Gutierrez ◽  
Kenneth C. Curley ◽  
...  

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