Abstract 17234: Elevated Atherosclerotic Biomarkers in Mice With Mild Blast Traumatic Brain Injury and Chronic Variable Stress

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Maureen N Hood ◽  
Vincent B Ho ◽  
Nisha Plavelil ◽  
Tao-Yiao Wu ◽  
Michaelson Luke ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Chronic Stress ◽  
Infrared Imaging ◽  
Imaging System ◽  
Blast Waves ◽  
Atherosclerotic Cardiovascular Disease ◽  
Western Blots ◽  
Blast Traumatic Brain Injury ◽  
Chronic Variable Stress

Introduction: Traumatic brain injury (TBI) and stress are significant health concerns that have atherosclerotic cardiovascular disease (ASCVD) effects. Stress and injury can elevate neurochemicals and hormones in the brain that lead to dysfunction of the hypothalamic-pituitary-adrenal axis and the autonomic nervous system increasing inflammation, which plays a role in the development of ASCVD. Animal models can provide a method of separating mild TBI (mTBI) from models of chronic stress. Hypothesis: We hypothesize that mild blast TBI (mbTBI) and chronic variable stress (CVS) will result in elevated ASCVD biomarkers in mice. Methods: Frozen hearts from C57BL/6J mice (8 weeks, N=16, 8 male/8 randomly cycling female) were obtained through an IACUC approved study. The C57BL/6J mice were part of a mild blast TBI (mbTBI) study utilizing a blast chamber to receive a short duration shock wave (<10 msec, mean peak pressure of blast waves 19.9 psi). A group was subjected to CVS for two weeks prior to the blast, plus one week after blast. All groups were followed for four weeks. Western Blots with relative expression (normalized) were performed using an infrared imaging system. ERK1, ERK2, Galactein 3, Endothelin-1, BDNF, NT-Pro-BNP, and NRG1. ANOVA with Tukey HSD correction and descriptive statistics were performed using SPSS with significance by α of 0.05. Results: ERK1: mbTBI and CVS (p<0.05). CVS +mbTBI to CVS (0.015)( p<0.05 ), compared to mbTBI (0.017). ERK2: mbTBI sham = 0.009, CVS only = 0.008, mbTBI only = 0.008 and CVS + mbTBI = 0.012. Galectin-3 (Gal-3): CVS only = 0.144, CVS+mbTBI = 0.168, mbTBI (0.114) to sham (0.111) ( p<0.05 ). NT-Pro-BNP: CVS+mbTBI = 0.168, sham 0.076. mbTBI alone (0.077) and CVS alone (0.078). NRG1: mbTBI (0.195) and mbTBI with CVS (0.178). CVS only group (0.157). ET-1: mbTBI sham = 0.068, CVS only = 0.080 mbTBI only = 0.084 and CVS+mbTBI = 0.134. BDNF: CVS only = 0.053, CVS+mbTBI = 0.069. Sham group (0.047), mbTBI (0.038). Conclusion: Our results on proteins related to a broad spectrum of vascular growth, innervation, function, inflammation and markers of atherosclerotic plaque development suggest that mbTBI and/or chronic stress may increase risk for developing early ASCVD.

scholarly journals SUN-477 Chronic Variable Stress Worsens Effects of Mild Blast Traumatic Brain Injury on the Stress Response

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Mario Oyola ◽  
Ashley Russell ◽  
Lauren Miller ◽  
Robert Handa ◽  
Tao-Yiao Wu
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Stress Response ◽  
Blast Traumatic Brain Injury ◽  
Chronic Variable Stress

scholarly journals Allocation of funding into blast injury-related research and blast traumatic brain injury between 2000 and 2019: analysis of global investments from public and philanthropic funders

2020 ◽  
pp. bmjmilitary-2020-001655
Author(s):  
J W Denny ◽  
R J Brown ◽  
M G Head ◽  
J Batchelor ◽  
A S Dickinson
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Open Data ◽  
Blast Injury ◽  
Included Study ◽  
Related Research ◽  
Blast Traumatic Brain Injury ◽  
Research Investment ◽  
Ear Injury ◽  
Injury Research

IntroductionThere is little systematic tracking or detailed analysis of investments in research and development for blast injury to support decision-making around research future funding.MethodsThis study examined global investments into blast injury-related research from public and philanthropic funders across 2000–2019. Research databases were searched using keywords, and open data were extracted from funder websites. Data collected included study title, abstract, award amount, funder and year. Individual awards were categorised to compare amounts invested into different blast injuries, the scientific approaches taken and analysis of research investment into blast traumatic brain injury (TBI).ResultsA total of 806 awards were identified into blast injury-related research globally, equating to US$902.1 million (m, £565.9m GBP). There was a general increase in year-on-year investment between 2003 and 2009 followed by a consistent decline in annual funding since 2010. Pre-clinical research received $671.3 m (74.4%) of investment. Brain-related injury research received $427.7 m (47.4%), orthopaedic injury $138.6 m (15.4%), eye injury $63.7 m (7.0%) and ear injury $60.5m (6.7%). Blast TBI research received a total investment of $384.3 m, representing 42.6% of all blast injury-related research. The U.S. Department of Defense funded $719.3 m (80%).ConclusionsInvestment data suggest that blast TBI research has received greater funding than other blast injury health areas. The funding pattern observed can be seen as reactive, driven by the response to the War on Terror, the rising profile of blast TBI and congressionally mandated research.

scholarly journals Imaging and serum biomarkers reflecting the functional efficacy of extended erythropoietin treatment in rats following infantile traumatic brain injury

2016 ◽  
Vol 17 (6) ◽  
pp. 739-755 ◽  
Author(s):  
Shenandoah Robinson ◽  
Jesse L. Winer ◽  
Justin Berkner ◽  
Lindsay A. S. Chan ◽  
Jesse L. Denson ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Diffusion Tensor ◽  
Elevated Serum ◽  
Serum Biomarkers ◽  
Receptor Expression ◽  
Acute Injury ◽  
Chronic Injury ◽  
Western Blots ◽  
Targeted Interventions

OBJECTIVE Traumatic brain injury (TBI) is a leading cause of death and severe morbidity for otherwise healthy full-term infants around the world. Currently, the primary treatment for infant TBI is supportive, as no targeted therapies exist to actively promote recovery. The developing infant brain, in particular, has a unique response to injury and the potential for repair, both of which vary with maturation. Targeted interventions and objective measures of therapeutic efficacy are needed in this special population. The authors hypothesized that MRI and serum biomarkers can be used to quantify outcomes following infantile TBI in a preclinical rat model and that the potential efficacy of the neuro-reparative agent erythropoietin (EPO) in promoting recovery can be tested using these biomarkers as surrogates for functional outcomes. METHODS With institutional approval, a controlled cortical impact (CCI) was delivered to postnatal Day (P)12 rats of both sexes (76 rats). On postinjury Day (PID)1, the 49 CCI rats designated for chronic studies were randomized to EPO (3000 U/kg/dose, CCI-EPO, 24 rats) or vehicle (CCI-veh, 25 rats) administered intraperitoneally on PID1–4, 6, and 8. Acute injury (PID3) was evaluated with an immunoassay of injured cortex and serum, and chronic injury (PID13–28) was evaluated with digitized gait analyses, MRI, and serum immunoassay. The CCI-veh and CCI-EPO rats were compared with shams (49 rats) primarily using 2-way ANOVA with Bonferroni post hoc correction. RESULTS Following CCI, there was 4.8% mortality and 55% of injured rats exhibited convulsions. Of the injured rats designated for chronic analyses, 8.1% developed leptomeningeal cyst–like lesions verified with MRI and were excluded from further study. On PID3, Western blot showed that EPO receptor expression was increased in the injured cortex (p = 0.008). These Western blots also showed elevated ipsilateral cortex calpain degradation products for αII-spectrin (αII-SDPs; p < 0.001), potassium chloride cotransporter 2 (KCC2-DPs; p = 0.037), and glial fibrillary acidic protein (GFAP-DPs; p = 0.002), as well as serum GFAP (serum GFAP-DPs; p = 0.001). In injured rats multiplex electrochemiluminescence analyses on PID3 revealed elevated serum tumor necrosis factor alpha (TNFα p = 0.01) and chemokine (CXC) ligand 1 (CXCL1). Chronically, that is, in PID13–16 CCI-veh rats, as compared with sham rats, gait deficits were demonstrated (p = 0.033) but then were reversed (p = 0.022) with EPO treatment. Diffusion tensor MRI of the ipsilateral and contralateral cortex and white matter in PID16–23 CCI-veh rats showed widespread injury and significant abnormalities of functional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD); MD, AD, and RD improved after EPO treatment. Chronically, P13–P28 CCI-veh rats also had elevated serum CXCL1 levels, which normalized in CCI-EPO rats. CONCLUSIONS Efficient translation of emerging neuro-reparative interventions dictates the use of age-appropriate preclinical models with human clinical trial–compatible biomarkers. In the present study, the authors showed that CCI produced chronic gait deficits in P12 rats that resolved with EPO treatment and that chronic imaging and serum biomarkers correlated with this improvement.

Severe Traumatic Brain Injury

2018 ◽  
Author(s):  
Ryan Martin ◽  
Lara Zimmermann ◽  
Kee D. Kim ◽  
Marike Zwienenberg ◽  
Kiarash Shahlaie
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
Severe Traumatic Brain Injury ◽  
Neurocritical Care ◽  
Secondary Brain Injury ◽  
Brain Oxygenation ◽  
Barbiturate Coma ◽  
Blast Traumatic Brain Injury ◽  
Penetrating Traumatic Brain Injury

Traumatic brain injury remains a leading cause of death and disability worldwide. Patients with severe traumatic brain injury are best treated with a multidisciplinary, evidence-based, protocol-directed approach, which has been shown to decrease mortality and improve functional outcomes. Therapy is directed at the prevention of secondary brain injury through optimizing cerebral blood flow and the delivery of metabolic fuel (ie, oxygen and glucose). This is accomplished through the measurement and treatment of elevated intracranial pressure (ICP), the strict avoidance of hypotension and hypoxemia, and in some instances, surgical management. The treatment of elevated ICP is approached in a protocolized, tiered manner, with escalation of care occurring in the setting of refractory intracranial hypertension, culminating in either decompressive surgery or barbiturate coma. With such an approach, the rates of mortality secondary to traumatic brain injury are declining despite an increasing incidence of traumatic brain injury. This review contains 3 figures, 5 tables and 69 reference Key Words: blast traumatic brain injury, brain oxygenation, cerebral perfusion pressure, decompressive craniectomy, hyperosmolar therapy, intracranial pressure, neurocritical care, penetrating traumatic brain injury, severe traumatic brain injury

Blast Traumatic Brain Injury Mechanisms

Neurotrauma ◽  
2018 ◽  
pp. 111-122
Author(s):  
Elizabeth McNeil ◽  
Zachary Bailey ◽  
Allison Guettler ◽  
Pamela VandeVord
Keyword(s):  
Traumatic Brain Injury ◽  
Finite Element ◽  
Brain Injury ◽  
Head Injury ◽  
Mechanism Of Injury ◽  
Primary Blast ◽  
Blast Traumatic Brain Injury ◽  
Injury Mechanisms ◽  
Biomechanical Investigation

Blast traumatic brain injury (bTBI) is a leading cause of head injury in soldiers returning from the battlefield. Primary blast brain injury remains controversial with little evidence to support a primary mechanism of injury. The four main theories described herein include blast wave transmission through skull orifices, direct cranial transmission, thoracic surge, and skull flexure dynamics. It is possible that these mechanisms do not occur exclusively from each other, but rather that several of them lead to primary blast brain injury. Biomechanical investigation with in-vivo, cadaver, and finite element models would greatly increase our understanding of bTBI mechanisms.

scholarly journals A Mouse Model of Repetitive Blast Traumatic Brain Injury Reveals Post-Trauma Seizures and Increased Neuronal Excitability

2020 ◽  
Vol 37 (2) ◽  
pp. 248-261 ◽  
Author(s):  
Vladislav Bugay ◽  
Eda Bozdemir ◽  
Fabio A. Vigil ◽  
Sang H. Chun ◽  
Deborah M. Holstein ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mouse Model ◽  
Neuronal Excitability ◽  
Blast Traumatic Brain Injury

Glibenclamide pretreatment protects against chronic memory dysfunction and glial activation in rat cranial blast traumatic brain injury

2017 ◽  
Vol 333 ◽  
pp. 43-53 ◽  
Author(s):  
Jesse A. Stokum ◽  
Kaspar Keledjian ◽  
Erik Hayman ◽  
Jason K. Karimy ◽  
Adam Pampori ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glial Activation ◽  
Memory Dysfunction ◽  
Blast Traumatic Brain Injury
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