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In Vitro Cortical Networks for Disease Modeling and Drug Evaluation

Description: In translational research, disease models in preclinical studies are used as media for discovery of drugs or novel therapeutics. Development of in vitro models for various neurological diseases that enable efficient pharmacological or toxicological screening has been ongoing but challenging. Recognizing the potential benefit of in vitro disease models, dysfunctions in the cortical neuronal networks were induced to mimic the functional pathology of neurological symptoms using microelectrode arrays. Two different disease states – tinnitusand excitotoxicity – were investigated and discussed. In this model, pentylenetetrazol-induced increase in spontaneous firing rate and synchrony in the auditory cortical networks was used as correlate of tinnitus. Potential tinnitus treatment drugs from several different classes – including the novel class of potassium channel openers – were screened and quantified. The potentialtherapeutic values of these drugs were also discussed as the basis for drug repurposing. Functional excitotoxicity was induced by cisplatin (a cancer drug that causes neurological sideeffects) and glutamate (the major excitatory neurotransmitter). As proof-of-principle that the model may contribute to expediting the development of therapeutics, cisplatin excitotoxicity wasprevented by the antioxidant D-methionine, while glutamate excitotoxicity was prevented by ceftriaxone (a modulator of a glutamate reuptake transporter). In the latter part of the study, with results linking two of the screened drugs L-carnitine and D-methionine to GABAA receptor activation, it was demonstrated that this model not only served as an efficient drug-screening platform, but can be utilized to functionally investigate the underlying mechanism of drugs. Inaddition, several practical or conceptual directions for future studies to improve on this in vitro disease model are suggested.
Date: December 2013
Creator: Wu, Calvin
Partner: UNT Libraries

In Vitro Exploration of Function Acrolein Toxicity with Cortical Neuronal Networks

Description: Acrolein is produced endogenously after traumatic brain injury (TBI) and is considered a primary mechanism for secondary damage occurring after TBI. We are using frontal cortex networks derived from mouse embryos and grown on microelectrode arrays in vitro to monitor the spontaneous activity of networks and the changes that occur after acrolein application. Networks exposed to acrolein exhibit a biphasic response profile. An initial increase in network activity, followed by a decrease to 100% activity loss in applications ≥ 50 µM. In applications below 50 µM, acrolein was not toxic but generated activity instability with coordinated but irregular population busts lasting for up to 6 days. The increase in activity preceding toxicity may be linked to a decrease in free spermine, a free radical scavenger that modulates Na+, K+, Ca+ channels as well as NMDA, Kainate, and AMPA receptors. Action potential wave shape analysis after 20 and 30 µM acrolein application revealed a concentration-dependent 15-33% increase in peak to peak amplitude within minutes after exposure. For the same concentrations of acrolein (50 µM), the time required to reach 100% activity loss (IT100) was longer in serum-free medium than in medium with 5% serum, in which IT100 values were reduced by a factor of 4. The greater toxicity in the presence of serum may be explained by acrolein adducts on serum proteins. These reaction products have been shown by other labs to be toxic in cell culture. This in vitro system could be used to expand biochemical analyses such as acrolein-induced spermine depletion and may provide an effective platform for investigating cell culture correlates of secondary TBI damage.
Date: May 2018
Creator: Durant, Stormy R
Partner: UNT Libraries

Archaeological and Biological Analysis of World War II Shipwrecks in the Gulf of Mexico: Artificial Reef Effect in Deep Water

Description: The objective of this research is to find, identify, and study each vessel that was a casualty of German U-boats. The second point of their research is to determine the biological effects of the boats on the environment.
Date: April 2007
Creator: Church, R.; Warren, D.; Cullimore, R.; Johnston, L.; Schroeder, W.; Patterson, W. et al.
Partner: UNT Libraries Government Documents Department

Safety of Autologous Umbilical Cord Blood Therapy for Acquired Sensorineural Hearing Loss in Children

Description: This article presents the results of a phase 1 clinical trial to evaluate the intravenous administration of human umbilical cord blood (hUCB) mononuclear fraction in infants and children with acquired sensorineural hearing loss (SNHL).
Date: June 18, 2018
Creator: Baumgartner, Linda S.; Moore, Ernest J.; Shook, David; Messina, Steven; Day, Mary Clare; Green, Jennifer et al.
Partner: UNT College of Public Affairs and Community Service