Therapeutic and Topographical Approaches for Improved Neural Electrode Biocompatibility

 产品说明： 大脑皮层内电极记录的神经元电信号已被人类患者用于与计算机通信和控制机器人肢体。可记录信号的信号质量和寿命不一致。越来越多的证据表明，神经炎症反应可能是持续获得高质量记录的主要障碍。许多故障模式可能影响长期记录稳定性和质量，包括：A）神经元活动减少; B）组织阻抗增加; C）电荷转移中断。传统上，微电极失效模式在很大程度上是相互独立研究的。然而，各种模式之间可能存在相当大的相互作用，因此很难将故障归因于单一机制。 目前的建议将联合收割机的卡帕多纳实验室（主要导师）的专业知识与CDA候选人的经验相结合。卡帕多纳博士的实验室先前已经证明，炎症衍生的活性氧使神经炎症和神经变性持续存在。为了减轻氧化应激水平并提高神经元活力，Capadona实验室使用了几种抗氧化剂，如白藜芦醇。他的实验室的研究表明，短期服用白藜芦醇可以减少最初的氧化应激和神经元变性，同时提高神经元的活力。然而，抗氧化方法不能抑制星形胶质细胞瘢痕形成，这已被证明会降低记录质量。相反，Ereifej博士已经表明，在纳米级水平上修饰电极材料的表面形貌可以减少急性神经胶质细胞炎症反应。这被认为是通过改变细胞粘附、迁移、活力， 分化和基因表达。因此，该建议的中心假设是，白藜芦醇和微电极表面的地形图案化的组合治疗施用将附加地改善从皮质内微电极获得的神经记录的质量和稳定性。 我们建议首先确定每天服用白藜芦醇在多大程度上改善皮层内电极神经记录的寿命和质量。这一目标将测试假设，即每天服用白藜芦醇将导致植入微电极的稳定神经信号，因为它减弱了神经炎症。接下来，我们将调查寿命和质量的皮质内电极神经记录地形修饰电极与白藜芦醇在体内管理和不。在这里，我们将测试的假设，即治疗与白藜芦醇和地形修改将是上级的任何一种治疗孤立，因为这些策略的目标是不同的成分，有害的中枢神经系统的生物材料植入的反应。 在整个拟定研究中，将针对具有形貌修饰和非修饰表面的稀释剂处理对照，评价具有形貌修饰和非修饰表面的白藜芦醇处理动物随时间推移获得的神经记录的寿命和质量（由活性通道数量及其信噪比定义）。此外，死后组织学将记录性能与氧化应激、神经保护、血脑屏障稳定性和神经胶质瘢痕形成相关联。这项研究旨在回答 临床相关问题，并有可能直接影响正在进行的和未来的非人灵长类动物和临床试验完成拟议的研究。Ereifej博士的职业发展计划与这项研究相结合，目标是培训成为一名领先的研究者，专注于研究疾病，损伤和神经系统疾病，以找到治疗和医疗器械治疗方法，以帮助患者的健康和长寿。

 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.