title: Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.
abstract: Implantable silicon microelectrode array technology is a useful technique for obtaining high-density, high-spatial resolution sampling of neuronal activity within the brain and holds promise for a wide range of neuroprosthetic applications. One of the limitations of the current technology is inconsistent performance in long-term applications. Although the brain tissue response is believed to be a major cause of performance degradation, the precise mechanisms that lead to failure of recordings are unknown. We observed persistent ED1 immunoreactivity around implanted silicon microelectrode arrays implanted in adult rat cortex that was accompanied by a significant reduction in nerve fiber density and nerve cell bodies in the tissue immediately surrounding the implanted silicon microelectrode arrays. Persistent ED1 up-regulation and neuronal loss was not observed in microelectrode stab controls indicating that the phenotype did not result from the initial mechanical trauma of electrode implantation, but was associated with the foreign body response. In addition, we found that explanted electrodes were covered with ED1/MAC-1 immunoreactive cells and that the cells released MCP-1 and TNF-alpha under serum-free conditions in vitro. Our findings suggest a potential new mechanism for chronic recording failure that involves neuronal cell loss, which we speculate is caused by chronic inflammation at the microelectrode brain tissue interface.
authors.affiliation: The Keck Center for Tissue Engineering, Department of Bioengineering, University of Utah, 20S 2030E Bldg. 570 Rm. 108, Salt Lake City, UT 84112, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Biran
authors.forename: David C
authors.initials: DC
authors.lastname: Martin
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Tresco
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000473:pathology*; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods; D053331:Ectodysplasins; D004567:Electrodes, Implanted / Q000009:adverse effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009281:Naphthalenes; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010082:Oxepins; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012825:Silicon / Q000009:adverse effects*; D013997:Time Factors
chemical_list: C461941:1-phenyl-1,4-epoxy-1H,4H-naphtho(1,8-de)(1,2)dioxepin; D016207:Cytokines; D053331:Ectodysplasins; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D009281:Naphthalenes; D016900:Neurofilament Proteins; D010082:Oxepins; D010751:Phosphopyruvate Hydratase; D012825:Silicon