title: The roles of blood-derived macrophages and resident microglia in the neuroinflammatory response to implanted intracortical microelectrodes.
abstract: Resident microglia and blood-borne macrophages have both been implicated to play a dominant role in mediating the neuroinflammatory response affecting implanted intracortical microelectrodes. However, the distinction between each cell type has not been demonstrated due to a lack of discriminating cellular markers. Understanding the subtle differences of each cell population in mediating neuroinflammation can aid in determining the appropriate therapeutic approaches to improve microelectrode performance. Therefore, the goal of this study is to characterize the role of infiltrating blood-derived cells, specifically macrophages, in mediating neuroinflammation following intracortical microelectrode implantation. Interestingly, we found no correlation between microglia and neuron populations at the microelectrode-tissue interface. On the other hand, blood-borne macrophages consistently dominated the infiltrating cell population following microelectrode implantation. Most importantly, we found a correlation between increased populations of blood-derived cells (including the total macrophage population) and neuron loss at the microelectrode-tissue interface. Specifically, the total macrophage population was greatest at two and sixteen weeks post implantation, at the same time points when we observed the lowest densities of neuronal survival in closest proximity to the implant. Together, our results suggest a dominant role of infiltrating macrophages, and not resident microglia, in mediating neurodegeneration following microelectrode implantation.
authors: Department of Biomedical Engineering, Case Western Reserve University, School of Engineering, 2071 Martin Luther King Jr. Drive, Wickenden Bldg, Cleveland OH 44106, USA; Louis Stokes Cleveland Veterans Affairs Medical Center, Rehabilitation Research and Development, Spinal Cord Injury Division, 10701 East Blvd. Mail Stop 151 AW/APT, Cleveland OH 44106, USA.
authors: Madhumitha
authors: M
authors: Ravikumar
authors: Department of Biomedical Engineering, Case Western Reserve University, School of Engineering, 2071 Martin Luther King Jr. Drive, Wickenden Bldg, Cleveland OH 44106, USA; Louis Stokes Cleveland Veterans Affairs Medical Center, Rehabilitation Research and Development, Spinal Cord Injury Division, 10701 East Blvd. Mail Stop 151 AW/APT, Cleveland OH 44106, USA.
authors: Smrithi
authors: S
authors: Sunil
authors: Department of Biomedical Engineering, Case Western Reserve University, School of Engineering, 2071 Martin Luther King Jr. Drive, Wickenden Bldg, Cleveland OH 44106, USA.
authors: James
authors: J
authors: Black
authors: Department of Biomedical Engineering, Case Western Reserve University, School of Engineering, 2071 Martin Luther King Jr. Drive, Wickenden Bldg, Cleveland OH 44106, USA; Department of Pediatrics, Case Western Reserve University School of Medicine, Wolstein Research Building 6528, 2103 Cornell Rd, Cleveland, OH 44106, USA.
authors: Deborah S
authors: DS
authors: Barkauskas
authors: Department of Pediatrics, Case Western Reserve University School of Medicine, Wolstein Research Building 6528, 2103 Cornell Rd, Cleveland, OH 44106, USA.
authors: Alex Y
authors: AY
authors: Haung
authors: Department of Neurosciences, Case Western Reserve University, School of Medicine, 10900 Euclid Ave, Sears Tower Bldg, Cleveland OH 44106, USA.
authors: Robert H
authors: RH
authors: Miller
authors: Department of Neurology, Case Western Reserve University, School of Medicine, 11100 Euclid Avenue, Sears Tower Bldg, Cleveland OH 44106, USA; Louis Stokes Cleveland Veterans Affairs Medical Center, Rehabilitation Research and Development, Spinal Cord Injury Division, 10701 East Blvd. Mail Stop 151 AW/APT, Cleveland OH 44106, USA.
authors: Stephen M
authors: SM
authors: Selkirk
authors: Department of Biomedical Engineering, Case Western Reserve University, School of Engineering, 2071 Martin Luther King Jr. Drive, Wickenden Bldg, Cleveland OH 44106, USA; Louis Stokes Cleveland Veterans Affairs Medical Center, Rehabilitation Research and Development, Spinal Cord Injury Division, 10701 East Blvd. Mail Stop 151 AW/APT, Cleveland OH 44106, USA. Electronic address: jeffrey.capadona@case.edu.
authors: Jeffrey R
authors: JR
authors: Capadona
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001812:Blood-Brain Barrier; D002465:Cell Movement; D004567:Electrodes, Implanted; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D008264:Macrophages / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008839:Microelectrodes; D017628:Microglia / Q000473:pathology*; D009474:Neurons / Q000378:metabolism; D019736:Prostheses and Implants
chemical_list: C485182:Cyan Fluorescent Protein; D007074:Immunoglobulin G; D049452:Green Fluorescent Proteins
keywords: Macrophage; Microelectrode; Microglia; Neuroinflammation