Novel approaches to counteracting the reactive tissue response to intracortical microelectrodes

Nnadozie I Onunkwo, Purdue University

Abstract

Through motor prosthesis research, breakthroughs have been made to greatly improve the quality of life for those suffering from spinal cord injuries and neurological diseases. By implanting microelectrodes into the motor cortex, scientists have been able to monitor neuronal activity using chronic cortical recordings and efficient neural decoding algorithms. These signals can be used to control prosthetic devices for accomplishing various tasks, such as neuronal control of a robotic arm or computer cursor. However, there is a general degradation in recorded signal quality over time, likely attributable to the cellular response to injury after implantation, including neuronal cell death and glial cell encapsulation via inflammatory cytokine production. These responses result in a decrease in signal-to-noise ratio (SNR) and an increase in impedance at electrode recordings sites. Possible methods to reducing neuronal cell death and glial cell encapsulation are to (1) encourage the growth of neuronal processes toward implanted electrodes and (2) reduce the upregulation of inflammatory cytokines following brain injury. Therefore, preliminary in vitro studies have been conducted to assess the feasibility of these methods. Constant DC electric fields of ∼21, ∼35, ∼52 mV/mm were applied to E17 rat cortical neurons for 12 hrs. Fields of ∼21 mV/mm significantly increased neurite length in all directions. This low, physiological DC field may be effective in inducing neuronal growth toward implanted microelectrodes, increasing SNR. We also demonstrated the ability of a cell-penetrating peptide (MK2i) to reduce MAPKAP kinase 2-mediated inflammatory cytokine release. In vitro experiments modeled a brain injury by treating 7-10 day old E17 cortical tri-cultures (neurons, microglia, and astrocytes) with TNF-α, followed by MK2i treatment. Immunohistochemical stains verified tri-culture cell growth and showed healthy cell morphology following MK2i treatments. ELISA and cytotoxicity assays showed that 0.5, 1 and 3 mM treatment with the MK2i significantly lowers interleukin-6 and interleukin-1β production after TNF-α inflammation and is also non-toxic to cells. Results suggest MK2i may reduce cellular response to indwelling microelectrodes by reducing inflammatory cytokine production, resulting in lowered impedance and more reliable long-term neuronal recordings. These in vitro results suggest possible methods for improving the long-term functionality of chronic intracortical microelectrodes.

Degree

Ph.D.

Advisors

Otto, Purdue University.

Subject Area

Neurosciences|Biomedical engineering

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