BBB leakage,astrogliosis, and tissue loss correlate with silicon microelectrode array recording performance |
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| Affiliation: | 1. Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907-1791, United States;2. Department of Biological Sciences, Purdue University, West Lafayette, IN 47907-1791, United States;1. Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr. Drive, Wickenden Bldg, Cleveland, OH 44106, USA;2. Advanced Platform Technology Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, 10701 East Blvd, 151 W/APT, Cleveland, OH 44106-1702, USA;3. Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, 1700 Fribourg, Switzerland;4. Virginia Tech, Department of Materials Science & Engineering & Macromolecules and Interfaces Institute, 445 Old Turner Street, 213 Holden Hall, Blacksburg, VA 24061, USA;5. Department of Macromolecular Science and Engineering, Case Western Reserve University, 2100 Adelbert Road, Kent Hale Smith Bldg, Cleveland, OH 44106-7202, USA;1. Bioengineering, University of Pittsburgh, United States;2. Center for the Neural Basis of Cognition, United States;3. McGowan Institute for Regenerative Medicine, University of Pittsburgh, United States;4. Division of Biology and Biological Engineering, California Institute of Technology, United States;5. Ophthalmology, University of Pittsburgh, United States;6. Biomedical Engineering, Carnegie Mellon University, United States;7. Neurological Surgery, University of Pittsburgh, United States;1. Bioengineering, University of Pittsburgh, United States;2. Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, United States;3. McGowan Institute for Regenerative Medicine, University of Pittsburgh, United States;4. NeuroTech Center of the University of Pittsburgh Brain Institute, United States;5. Radiology, University of Pittsburgh, United States;6. Neurobiology, University of Pittsburgh, United States;1. Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States;2. Center for Neural Basis of Cognition, Pittsburgh, PA, United States;3. McGowan Institute for Regenerative Medicine, Pittsburgh, PA, United States;4. Neuroscience Imaging Center, University of Pittsburgh, Pittsburgh, PA, United States;5. Department of Radiology, University of Pittsburgh, Pittsburgh, PA, United States;6. Division of Biology and Biological Engineering, California Institute of Technology, United States;1. Bioengineering, University of Pittsburgh, United States;2. Center for the Neural Basis of Cognition, United States;3. McGowan Institute for Regenerative Medicine, University of Pittsburgh, United States;4. Neurotech Center of the University of Pittsburgh Brain Institute, United States;5. Chemistry, University of Pittsburgh, United States;6. Radiology, University of Pittsburgh, United States |
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| 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. |
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| Keywords: | Foreign body response Electrode Inflammation Neural prosthesis Blood flow Brain |
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