Browsing by Author "Sajja, Venkata Siva Sai Sujith"
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- Blasted Flies and Nanoparticles for TBIHockey, 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.
- Cerium Oxide Nanoparticles Improve Outcome after In Vitro and In Vivo Mild Traumatic Brain InjuryBailey, Zachary S.; Nilson, Eric; Bates, John A.; Oyalowo, Adewole; Hockey, Kevin S.; Sajja, Venkata Siva Sai Sujith; Thorpe, Chevon N.; Rogers, Heidi; Dunn, Bryce; Frey, Aaron S.; Billings, Marc J.; Sholar, Christopher A.; Hermundstad, Amy; Kumar, Challa; VandeVord, Pamela J.; Rzigalinski, Beverly A. (2020-06-15)Mild traumatic brain injury results in aberrant free radical generation, which is associated with oxidative stress, secondary injury signaling cascades, mitochondrial dysfunction, and poor functional outcome. Pharmacological targeting of free radicals with antioxidants has been examined as an approach to treatment, but has met with limited success in clinical trials. Conventional antioxidants that are currently available scavenge a single free radical before they are destroyed in the process. Here, we report for the first time that a novel regenerative cerium oxide nanoparticle antioxidant reduces neuronal death and calcium dysregulation after in vitro trauma. Further, using an in vivo model of mild lateral fluid percussion brain injury in the rat, we report that cerium oxide nanoparticles also preserve endogenous antioxidant systems, decrease macromolecular free radical damage, and improve cognitive function. Taken together, our results demonstrate that cerium oxide nanoparticles are a novel nanopharmaceutical with potential for mitigating neuropathological effects of mild traumatic brain injury and modifying the course of recovery.
- Enduring deficits in memory and neuronal pathology after blast-induced traumatic brain injurySajja, Venkata Siva Sai Sujith; Hubbard, W. Brad; Hall, Christina S.; Ghoddoussi, Farhad; Galloway, Matthew P.; VandeVord, Pamela J. (Nature Publishing Group, 2015-11-05)
- Impaired Behavioral and Pathological Outcomes Following Blast NeurotraumaSajja, Venkata Siva Sai Sujith (Virginia Tech, 2013-08-30)Blast-induced neurotrauma (BINT) is a major societal concern due to the complex expression of neuropathological disorders after exposure to blast. Disruptions in neuronal function, proximal in time to the blast exposure, may eventually contribute to the late emergence of the clinical deficits. Besides complications with differential clinical diagnosis, the biomolecular mechanism underlying BINT that gives rise to cognitive deficits is poorly understood. Some pre-clinical studies have demonstrated cognitive deficits at an acute stage following blast overpressure (BOP) exposure. However, the behavioral deficit type (e.g., short term memory) and the mechanism underlying injury prognosis that onsets the cognitive deficits remains to be further investigated. An established rodent model of blast neurotrauma was used in order to study impaired behavioral and neuropathological outcomes following blast. Anesthetized rats were exposed to a calibrated BOP using a blast simulator while control animals were not exposed to BOP. Behavioral changes in short term memory and anxiety were assessed with standard behavioral techniques (novel objected recognition paradigm and light and dark box test) at acute and chronic stages (range: 3 hours -- 3 months). In addition, brains were assayed for neurochemical changes using proton magnetic resonance spectroscopy (MRS) and neuropathology with immunohistochemistry in cognitive regions of brain (hippocampus, amygdala, frontal cortex and nucleus accumbens) Early metabolic changes and oxidative stress were observed along with a compromise in energy metabolism associated with sub-acute (7 days following BOP exposure) active neurodegeneration and glial scarring. Data suggested GABA shunting pathway was activated and phospholipase A2 regulated arachadonic acid pathway may be involved in cellular death cascades. In addition, increased myo-inositol levels in medial pre-frontal cortex (PFC) further supported the glial scarring and were associated with impaired working memory at a sub-acute stage (7 days) following BOP exposure. Chronic working memory issues and anxiety associated behavior could be related to chronic activation of microglia in hippocampus and astrocytes in amygdala respectively. Furthermore, these results from MRS could be directly translated into clinical studies to provide a valuable insight into diagnosis of BINT, and it is speculated that gliosis associated markers (myo-inositol) may be a potential biomarker for blast-induced memory impairment.
- Role of Glia in Memory Deficits Following Traumatic Brain Injury: Biomarkers of Glia DysfunctionSajja, Venkata Siva Sai Sujith; Hlavac, Nora; VandeVord, Pamela J. (Frontiers Media S.A., 2016-02-29)Historically, glial cells have been recognized as a structural component of the brain. However, it has become clear that glial cells are intimately involved in the complexities of neural networks and memory formations. Astrocytes, microglia, and oligodendrocytes have dynamic responsibilities which substantially impact neuronal function and activities. Moreover, the importance of glia following brain injury has come to the forefront in discussions to improve axonal regeneration and functional recovery. The numerous activities of glia following injury can either promote recovery or underlie the pathobiology of memory deficits. This review outlines the pathological states of glial cells which evolve from their positive supporting roles to those which disrupt synaptic function and neuroplasticity following injury. Evidence suggests that glial cells interact extensively with neurons both chemically and physically, reinforcing their role as pivotal for higher brain functions such as learning and memory. Collectively, this mini review surveys investigations of how glial dysfunction following brain injury can alter mechanisms of synaptic plasticity and how this may be related to an increased risk for persistent memory deficits. We also include recent findings that demonstrate new molecular avenues for clinical biomarker discovery.