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Browsing by Author "Hubbard, W. Brad"

Now showing 1 - 5 of 5
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    Blasted Flies and Nanoparticles for TBI
    Hockey, Kevin S.; Sholar, Christopher A.; Sajja, Venkata Siva Sai Sujith; Hubbard, W. Brad; Thorpe, Chevon; VandeVord, Pamela J.; Rzigalinski, Beverly A. (Brain Injuries and Biomechanics Symposium, 2013-09-19)
    This presentation briefly summaries two major areas of work in our lab, development of a Drosophila model of blast injury and treatment of traumatic brain injury (TBI) with cerium oxide nanoparticles. First, we discuss the design, methodology, and results for the Drosophila blast model, and its relevance to human head injury. Briefly, we found that the Drosophila model was able to reproduce the decreased lifespan and early death seen in military personnel exposed to repetitive mild blast and NFL players exposed to repeated mild head injury. Next we discuss our in vitro and in vivo work with cerium oxide nanoparticles as neuroprotective and regenerative agents for treatment of TBI. Using a tissue culture model for TBI, we found that cerium oxide nanoparticles, delivered up to 6 hrs. post-injury, improved neuronal survival and maintained near-normal glutamate signaling in neurons of mixed organotypic brain cell cultures. In vivo, we found that delivery of cerium oxide nanoparticles prior to lateral fluid percussion brain injury in the rat, improved motor performance, learning and memory.
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    Distinguishing the Unique Neuropathological Profile of Blast Polytrauma
    Hubbard, W. Brad; Greenberg, Shaylen; Norris, Carly; Eck, Joseph; Lavik, Erin; VandeVord, Pamela J. (Hindawi, 2017-03-23)
    Traumatic brain injury sustained after blast exposure (blast-induced TBI) has recently been documented as a growing issue for military personnel. Incidence of injury to organs such as the lungs has decreased, though current epidemiology still causes a great public health burden. In addition, unprotected civilians sustain primary blast lung injury (PBLI) at alarming rates. Often, mild-to-moderate cases of PBLI are survivable with medical intervention, which creates a growing population of survivors of blast-induced polytrauma (BPT) with symptoms from blast-induced mild TBI (mTBI). Currently, there is a lack of preclinical models simulating BPT, which is crucial to identifying unique injury mechanisms of BPT and its management. To meet this need, our group characterized a rodent model of BPT and compared results to a blast-induced mTBI model. Open field (OF) performance trials were performed on rodents at 7 days after injury. Immunohistochemistry was performed to evaluate cellular outcome at day seven following BPT. Levels of reactive astrocytes (GFAP), apoptosis (cleaved caspase-3 expression), and vascular damage (SMI-71) were significantly elevated in BPT compared to blast-induced mTBI. Downstream markers of hypoxia (HIF-1α and VEGF) were higher only after BPT. This study highlights the need for unique therapeutics and prehospital management when handling BPT.
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    Enduring deficits in memory and neuronal pathology after blast-induced traumatic brain injury
    Sajja, Venkata Siva Sai Sujith; Hubbard, W. Brad; Hall, Christina S.; Ghoddoussi, Farhad; Galloway, Matthew P.; VandeVord, Pamela J. (Nature Publishing Group, 2015-11-05)
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    Hemostatic nanoparticles increase survival, mitigate neuropathology and alleviate anxiety in a rodent blast trauma model
    Hubbard, W. Brad; Lashof-Sullivan, Margaret; Greenberg, Shaylen; Norris, Carly; Eck, Joseph; Lavik, Erin; VandeVord, Pamela J. (Springer Nature, 2018-07-13)
    Explosions account for 79% of combat related injuries and often lead to polytrauma, a majority of which include blast-induced traumatic brain injuries (bTBI). These injuries lead to internal bleeding in multiple organs and, in the case of bTBI, long term neurological deficits. Currently, there are no treatments for internal bleeding beyond fluid resuscitation and surgery. There is also a dearth of treatments for TBI. We have developed a novel approach using hemostatic nanoparticles that encapsulate an anti-inflammatory, dexamethasone, to stop the bleeding and reduce inflammation after injury. We hypothesize that this will improve not only survival but long term functional outcomes after blast polytrauma. Poly(lactic-co-glycolic acid) hemostatic nanoparticles encapsulating dexamethasone (hDNPs) were fabricated and tested following injury along with appropriate controls. Rats were exposed to a single blast wave using an Advanced Blast Simulator, inducing primary blast lung and bTBI. Survival was elevated in the hDNPs group compared to controls. Elevated anxiety parameters were found in the controls, compared to hDNPs. Histological analysis indicated that apoptosis and blood-brain barrier disruption in the amygdala were significantly increased in the controls compared to the hDNPs and sham groups. Immediate intervention is crucial to mitigate injury mechanisms that contribute to emotional deficits.
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    Investigating Injury Pathology of Blast-induced Polytrauma and Assessing the Therapeutic Role of Hemostatic Nanoparticles after Blast Exposure
    Hubbard, W. Brad (Virginia Tech, 2016-09-26)
    Explosions cause the majority of injuries in the current conflicts, accounting for 79% of combat related injuries (Ramasamy et al. 2008). Blast overpressure from explosions can cause barotrauma to the lungs and the brain. Blast-induced mild traumatic brain injury has been labeled the "signature wound" of current military conflicts in Iraq and Afghanistan (Snell and Halter 2010). In addition to elevated number of blast-induced traumatic brain injuries due to increased military conflicts overseas and the usage of improvised explosive devices, the incidence of blast-induced polytrauma has risen due to the prevalence of terrorist events around the world (Arnold et al. 2004, Rodoplu et al. 2004). Blast-induced polytrauma is a major concern as lung injury can cause immediate mortality and brain injury causes long-lasting neurocognitive impairment. There is a critical lack of understanding the pathology of blast-induced polytrauma since the needs are multifaceted and therefore few options for treatment. Thus, the research presented in this dissertation required the development of a military-relevant blast polytrauma model to examine injury pathology and subsequently study the effects of hemostatic nanoparticle therapy after blast-induced polytrauma. The pre-clinical model was characterized and static overpressure thresholds were determined for lethality risk. It was confirmed to have many of the classic hallmarks of primary blast lung injury (PBLI), as well as blast-induced neurotrauma (BINT) (Clemedson 1950). Global hemorrhaging was found in the lungs and well as reduced oxygen saturation. Markers of astrogliosis and blood-brain barrier disruption were examined in the amygdala after blast. The novel nanoparticle configuration (hemostatic dexamethasone-loaded nanoparticles (hDNP) functionalized with a peptide that binds with activated platelets) was investigated and hypothesized to increase survival, reduce cellular injury and reduce anxiety-like disorders after blast polytrauma. After investigating hDNP, it was found that the hDNP treatment benefited survival percentage after injury as well as reduced percent hemorrhage in the lungs and improved physiology. Elevated anxiety parameters found in the controls were lower as compared to the hDNP group. Glial fibrillary acidic protein (GFAP) and cleaved caspase-3 were significantly elevated in the controls compared to the hDNP group in the amygdala. SMI-71 was also significantly elevated with the hDNP and hemostatic nanoparticle (hNP) treatments, similar to sham. In addition to the nanoparticles offering immediate life-saving qualities, administration of hemostatic nanoparticles improved amygdala pathology attributed to secondary mechanisms of blast injury, including blood-brain barrier disruption. This model of polytrauma can serve as a foundation for detailed pathological studies as well as testing therapeutics for injury modalities. References (Abstract) Arnold, J. L., P. Halpern, M. C. Tsai and H. Smithline (2004). "Mass casualty terrorist bombings: a comparison of outcomes by bombing type." Ann Emerg Med 43(2): 263-273. Clemedson, C. J., Granstom, S.A. (1950). "Studies on the genesis of "rib markings" in lung blast injury." Acta Physiol Scand. 21: 131-144. Ramasamy, A., S. E. Harrisson, J. C. Clasper and M. P. Stewart (2008). "Injuries from roadside improvised explosive devices." J Trauma 65(4): 910-914. Rodoplu, U., Arnold, J. L., Tokyay, R., Ersoy, G., Cetiner, S., Yucel, T. (2004) "Mass-casualty terrorist bombings in Istanbul, Turkey, November 2003: reports of the events and the prehospital emergency response." Prehosp Disaster Med 19(2):133-145. Snell, F. I. and M. J. Halter (2010). "A signature wound of war: mild traumatic brain injury." J Psychosoc Nurs Ment Health Serv 48(2): 22-28.