Therapeutic and Topographical Approaches for Improved Neural Electrode Biocompatibility

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 DESCRIPTION: Electrical signals recorded from neurons by intracortical electrodes have been used by human patients to communicate with computers and to control robotic limbs. The signal quality and longevity of recordable signals are inconsistent. There is increasing evidence indicating that the neuro-inflammatory response may be a primary hurdle to consistently obtaining high quality recordings. A number of failure modes likely influence chronic recording stability and quality including: A) reduced neuronal activity; B) increased tissue impedance; C) disrupted charge transfer. Traditionally, microelectrode failure modes have largely been studied independently from one another. However, there is likely considerable interplay among the various modes making it difficult to attribute failure to a single mechanism. The current proposal will combine the expertise of the Capadona Lab (Primary Mentor) with the experience of the CDA candidate. Dr. Capadona's lab has previously demonstrated that inflammatory- derived reactive oxygen species perpetuates neuroinflammation and neurodegeneration. In order to alleviate the level of oxidative stress and improve neuronal viability, the Capadona lab has utilized several anti-oxidants, such as resveratrol. Studies from his lab have shown short-term administration of resveratrol reduces initial oxidative stress and neuron degeneration while improving neuronal viability. However, antioxidative approaches fail to inhibit astrocytic scar formation, which has been shown to decrease recording quality. In contrast, Dr. Ereifej has shown that modification of the surface topography of electrode materials on a nanoscale level reduces the acute glial cell inflammatory response. This is thought to work by altering cellular adhesion, migration, viability, differentiation, and gene expression. Therefore, the central hypothesis to this proposal is that a combined therapeutic administration of Resveratrol and topographical patterning of microelectrode surfaces will additively improve the quality and stability of neural recordings obtained from intracortical microelectrodes. We propose to first determine the extent to which daily administration of resveratrol improves the longevity and quality of intracortical electrode neural recordings. This aim will test the hypothesis that daily administration of Resveratrol will result in stable neural signal from implanted microelectrodes because it attenuates neuroinflammation. Next, we will investigate the longevity and quality of intracortical electrode neural recordings to topographically modified electrodes with and without administration of Resveratrol in vivo. Here we will test the hypothesis that the treatment with Resveratrol and topographic modification will be superior to either treatment in isolation because these strategies target different components of a detrimental CNS response to biomaterial implantation. Throughout the proposed study, resveratrol-treated animals, with topographically modified and non- modified surfaces, will be evaluated against diluent-treated controls with topographically modified and non-modified surfaces, for the longevity and quality of obtained neural recordings defined by the number of active channels and their signal-to-noise ratio, over time. Further, post-mortem histology will correlate recording performance to oxidative stress, neuroprotection, blood-brain barrier stability and glial scarring. This study is designed to answer clinically-relevant questions, and has the potential to directly impact ongoing and future non-human primate and clinical trials by the completion of the proposed study. This research is integrated with Dr. Ereifej's career development plan with the goal of training to become a leading investigator, focusing on studying diseases, injuries, and disorders of the nervous systems in order to find therapeutic and medical device treatments to aid in the wellbeing and longevity of patients' lives.