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Title: Chronic Intracortical Electrodes: Modulation of the Blood-brain Barrier and Functional Implications
Committee:
Dr. Ravi Bellamkonda, BME, Chair , Advisor
Dr. Robert Butera, ECE, Co-Advisor
Dr. Stephen DeWeerth, ECE
Dr. Thomas Barker, BME
Dr. Garrett Stanley, BME
Dr. Themis Kyriakides, Yale
Abstract:
Brain machine interfaces have the potential to connect patients living with paralysis to prosthetics and devices, dramatically improving quality of life. Intracortical electrodes provide the electrode-tissue interface and record action potentials from neurons. Over time, the strength of the recorded action potentials diminishes, making repeat trials and device control difficult. Local neurodegeneration has been identified at the electrode interface, and a negative correlation was found between recording performance and blood-brain barrier (BBB) breach. Here we administered a therapeutic inhibitor to modulate the BBB in an electrode implant model, while evaluating the functional electrophysiology. We also sought to better understand the molecular cues in the electrode implant model and correlated electrophysiology and mRNA at a chronic time point.
Specifically, the CCL2/CCR2 pathway was inhibited to prevent pro-inflammatory monocytes recruitment to the electrode interface and to also modulate the BBB. Functional Michigan electrodes were implanted for 2 and 12 weeks and administered a CCR2 antagonist. The number of animals with active recording electrodes was increased at 12 weeks when compared to controls, and histological outcomes were improved at 2 weeks in the treatment group. Then, in a chronic (>12 weeks) microwire model, mechanisms regulating the BBB, neuroinflammation, leukocyte infiltration, and inflammation were analyzed at 1 and 14 weeks. A significant correlation was found between SNR and PDGFR-β expression, suggesting a potential pathway to regulate for improved recording performance. The significance of this work is the increased understanding of the biological mechanisms at play in a functional, intracortical electrode implant model.
