Browsing by Author "Rzigalinski, Beverly A."

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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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    Cerium Oxide Nanoparticles Improve Outcome after In Vitro and In Vivo Mild Traumatic Brain Injury
    Bailey, 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.
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    Dopamine Stimulates Propagation of Toxoplasma gondii Tachyzoites in Human Fibroblast and Primary Neonatal Rat Astrocyte Cell Cultures
    Strobl, Jeannine S.; Goodwin, David G.; Rzigalinski, Beverly A.; Lindsay, David S. (American Society of Parasitology, 2012-12-01)
    Toxoplasma gondii is an obligate intracellular parasite often found in the brain of humans. Research has shown a correlation between prevalence of antibody titers to T. gondii and psychological illness in humans. Recent studies indicate that individuals seropositive for T. gondii antibodies are more likely to develop psychotic disorders including schizophrenia, which is associated with changes in the dopamine neurotransmitter system. Dopamine in the brain may play a role in proliferation, chemoattraction, infection efficiency, or stage conversion of T. gondii. Because tachyzoites are the first developmental stage to reach the brain, the present study was conducted to determine the effects of dopamine on their development in vitro. In human fibroblast host cells, dopamine was added at either 100 nM or 250 nM to cell culture media, and the numbers of tachyzoites produced at 48 hr were determined and compared to vehicle-treated controls. An increase of tachyzoite numbers and increased destruction in cell monolayer were observed at both concentrations of dopamine. Dopamine used at 250 nM caused a significant (P < 0.05) increase in tachyzoites counts compared to controls. Dopamine antagonists (10 mu M) did not significantly alter dopamine-stimulated tachyzoite production in human fibroblasts. In primary neonatal rat astrocyte cell cultures, dopamine (200 mu M) significantly (P < 0.05) increased numbers of intracellular tachyzoites after 24 hr. The role that this increase plays in tachyzoite production under the stimulus of dopamine in the modulation of neural infection in humans awaits further studies.
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    Genomic divergence and adaptive convergence in Drosophila simulans from Evolution Canyon, Israel
    Kang, Lin; Rashkovetsky, Eugenia; Michalak, Katarzyna; Garner, Harold R.; Mahaney, James E.; Rzigalinski, Beverly A.; Korol, Abraham B.; Nevo, Eviatar; Michalak, Pawel (2019-06-11)
    Biodiversity refugia formed by unique features of the Mediterranean arid landscape, such as the dramatic ecological contrast of "Evolution Canyon," provide a natural laboratory in which local adaptations to divergent microclimate conditions can be investigated. Significant insights have been provided by studies of Drosophila melanogaster diversifying along the thermal gradient in Evolution Canyon, but a comparative framework to survey adaptive convergence across sister species at the site has been lacking. To fill this void, we present an analysis of genomic polymorphism and evolutionary divergence of Drosophila simulans, a close relative of Drosophila melanogaster with which it co-occurs on both slopes of the canyon. Our results show even deeper interslope divergence in D. simulans than in D. melanogaster, with extensive signatures of selective sweeps present in flies from both slopes but enhanced in the population from the hotter and drier south-facing slope. Interslope divergence was enriched for genes related to electrochemical balance and transmembrane transport, likely in response to increased selection for dehydration resistance on the hotter slope. Both species shared genomic regions that underwent major selective sweeps, but the overall level of adaptive convergence was low, demonstrating no shortage of alternative genomic solutions to cope with the challenges of the microclimate contrast. Mobile elements were a major source of genetic polymorphism and divergence, affecting all parts of the genome, including coding sequences of mating behavior-related genes.