Browsing by Author "Knaack, Gretchen Linnea"
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Item In Vitro and In Vivo Biocompatibility Testing of Silicon Carbide for Neural Interfaces(2014-08) Knaack, Gretchen Linnea; Knaack, Gretchen Linnea; Pancrazio, Joseph J.This dissertation demonstrates the biocompatibility of amorphous silicon carbide for implementation with neural interfaces. To evaluate this capacity in vitro, frontal cortex networks cultured on microelectrode arrays were established and assessed pharmacologically by investigating the neurotoxic effects of ω-agatoxin. This valuable platform was then implemented as a functional compliment for the live/dead assay to test biomaterials in more sensitive manner. Finally, this assay was utilized to test the biocompatibility of different variations of silicon carbide for the possible use with neural interfaces. Since amorphous silicon carbide did not reduce spontaneous network firing rate in vitro, it was then examined in vivo. Standard silicon devices were coated with a thin film of amorphous silicon carbide and simultaneously implanted with silicon devices into the primary motor cortex of rats for either four or eight weeks. The neuroinflammatory reaction was then compared between the materials through device capture immunohistochemistry. NeuN, GFAP, CD68 and DAPI all displayed an increase in labeling from four to eight weeks of implantation. The more intense fluorescence of CD68 and DAPI at eight weeks was only located at distances proximal to devices, whereas NeuN and GFAP exhibited an overall enhancement. However, a decrease in NeuN labeling was still observed within 0-30µm of the device irrespective of the implant duration. Although these findings were independent of material, tissue implanted with amorphous silicon carbide did have a reduction of GFAP labeling within 0-10µm compared to tissue implanted with silicon. This occurred regardless of implant time. The in vitro and in vivo data jointly support the notion that the addition of amorphous silicon carbide to the standard silicon probe is biocompatible and decreases the neuroinflammatory response to cortical implants by reducing the intensity of GFAP adjacent to the device.Item The Effects of Chronic Unpredictable Stress on the Ability to Extinguish Fear: Zinc as a Mediator(2012-02-01) Knaack, Gretchen Linnea; Knaack, Gretchen Linnea; Flinn, Jane M.Chronic stress can be deleterious to the brain and it is the unpredictability of these stressors that fails to permit habituation, the effects of which are exhibited through maladaptive behaviors such as Post Traumatic Stress Disorder (PTSD). Implementing a chronic unpredictable stress (CUS) paradigm as an animal model of PTSD may facilitate the examination of possible mechanisms relating prolonged stress to the cognitive deficits frequently observed. One factor may be zinc because it is decreased in the blood while increased in the brain during stress, and it has been previously demonstrated that excess zinc in the brain causes learning and memory deficits. To ascertain this possibility rats were raised pre- and post-natally on supplemented zinc water for four months, administered a 21 day CUS paradigm, and then underwent fear conditioning. Post stress blood samples were also analyzed. Results determined that excess zinc rats displayed learning and memory deficits on the ability to extinguish fear and recall that extinction 24 hours later. CUS decreased the level of zinc in the blood for animals that drank lab water, but increased the amount of zinc in blood for animals that were supplemented with zinc. Furthermore, there was a positive correlation between the level of zinc in the blood and the ability to extinguish fear. These data suggest that zinc may be a mediator between chronic stress and anxiety disorders.