title: Nanoscale laminin coating modulates cortical scarring response around implanted silicon microelectrode arrays.
abstract: Neural electrodes could significantly enhance the quality of life for patients with sensory and/or motor deficits as well as improve our understanding of brain functions. However, long-term electrical connectivity between neural tissue and recording sites is compromised by the development of astroglial scar around the recording probes. In this study we investigate the effect of a nanoscale laminin (LN) coating on Si-based neural probes on chronic cortical tissue reaction in a rat model. Tissue reaction was evaluated after 1 day, 1 week, and 4 weeks post-implant for coated and uncoated probes using immunohistochemical techniques to evaluate activated microglia/macrophages (ED-1), astrocytes (GFAP) and neurons (NeuN). The coating did not have an observable effect on neuronal density or proximity to the electrode surface. However, the response of microglia/macrophages and astrocytes was altered by the coating. One day post-implant, we observed an approximately 60% increase in ED-1 expression near LN-coated probe sites compared with control uncoated probe sites. Four weeks post-implant, we observed an approximately 20% reduction in ED-1 expression along with an approximately 50% reduction in GFAP expression at coated relative to uncoated probe sites. These results suggest that LN has a stimulatory effect on early microglia activation, accelerating the phagocytic function of these cells. This hypothesis is further supported by the increased mRNA expression of several pro-inflammatory cytokines (TNF-alpha, IL-1 and IL-6) in cultured microglia on LN-bound Si substrates. LN immunostaining of coated probes immediately after insertion and retrieval demonstrates that the coating integrity is not compromised by the shear force during insertion. We speculate, based on these encouraging results, that LN coating of Si neural probes could potentially improve chronic neural recordings through dispersion of the astroglial scar.
authors.affiliation: Neurological Biomaterials and Therapeutics, Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, 313 Ferst Drive, Atlanta, GA 30332, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: George C
authors.initials: GC
authors.lastname: McConnell
authors.forename: Ravi V
authors.initials: RV
authors.lastname: Bellamkonda
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology*; D002921:Cicatrix / Q000473:pathology / Q000517:prevention & control*; D017931:DNA Primers; D004567:Electrodes, Implanted / Q000009:adverse effects*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D005911:Gliosis / Q000473:pathology; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007797:Laminin / Q000494:pharmacology*; D008297:Male; D008839:Microelectrodes / Q000009:adverse effects*; D008855:Microscopy, Electron, Scanning; D036103:Nanotechnology; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D011094:Polyethyleneimine / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012825:Silicon / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D017931:DNA Primers; D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1; D015850:Interleukin-6; D007797:Laminin; D014409:Tumor Necrosis Factor-alpha; D011094:Polyethyleneimine; D012825:Silicon