title: BBB leakage, astrogliosis, and tissue loss correlate with silicon microelectrode array recording performance.
abstract: The clinical usefulness of brain machine interfaces that employ penetrating silicon microelectrode arrays is limited by inconsistent performance at chronic time points. While it is widely believed that elements of the foreign body response (FBR) contribute to inconsistent single unit recording performance, the relationships between the FBR and recording performance have not been well established. To address this shortfall, we implanted 4X4 Utah Electrode Arrays into the cortex of 28 young adult rats, acquired electrophysiological recordings weekly for up to 12 weeks, used quantitative immunohistochemical methods to examine the intensity and spatial distribution of neural and FBR biomarkers, and examined whether relationships existed between biomarker distribution and recording performance. We observed that the FBR was characterized by persistent inflammation and consisted of typical biomarkers, including presumptive activated macrophages and activated microglia, astrogliosis, and plasma proteins indicative of blood-brain-barrier disruption, as well as general decreases in neuronal process distribution. However, unlike what has been described for recording electrodes that create only a single penetrating injury, substantial brain tissue loss generally in the shape of a pyramidal lesion cavity was observed at the implantation site. Such lesions were also observed in stab wounded animals indicating that the damage was caused by vascular disruption at the time of implantation. Using statistical approaches, we found that blood-brain barrier leakiness and astrogliosis were both associated with reduced recording performance, and that tissue loss was negatively correlated with recording performance. Taken together, our data suggest that a reduction of vascular damage at the time of implantation either by design changes or use of hemostatic coatings coupled to a reduction of chronic inflammatory sequela will likely improve the recording performance of high density intracortical silicon microelectrode arrays over long indwelling periods and lead to enhanced clinical use of this promising technology.
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, UT, USA.
authors.forename: Nicholas F
authors.initials: NF
authors.lastname: Nolta
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, UT, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Christensen
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, UT, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Crane
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, UT, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Skousen
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, UT, USA. Electronic address: patrick.tresco@utah.edu.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Tresco
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D001812:Blood-Brain Barrier; D005911:Gliosis / Q000503:physiopathology*; D008297:Male; D008839:Microelectrodes; D051381:Rats; D017207:Rats, Sprague-Dawley; D012825:Silicon
chemical_list: D012825:Silicon
keywords: Blood flow; Brain; Electrode; Foreign body response; Inflammation; Neural prosthesis