title: Neuroadhesive L1 coating attenuates acute microglial attachment to neural electrodes as revealed by live two-photon microscopy.
abstract: Implantable neural electrode technologies for chronic neural recordings can restore functional control to paralysis and limb loss victims through brain-machine interfaces. These probes, however, have high failure rates partly due to the biological responses to the probe which generate an inflammatory scar and subsequent neuronal cell death. L1 is a neuronal specific cell adhesion molecule and has been shown to minimize glial scar formation and promote electrode-neuron integration when covalently attached to the surface of neural probes. In this work, the acute microglial response to L1-coated neural probes was evaluated in vivo by implanting coated devices into the cortex of mice with fluorescently labeled microglia, and tracking microglial dynamics with multi-photon microscopy for the ensuing 6 h in order to understand L1's cellular mechanisms of action. Microglia became activated immediately after implantation, extending processes towards both L1-coated and uncoated control probes at similar velocities. After the processes made contact with the probes, microglial processes expanded to cover 47.7% of the control probes' surfaces. For L1-coated probes, however, there was a statistically significant 83% reduction in microglial surface coverage. This effect was sustained through the experiment. At 6 h post-implant, the radius of microglia activation was reduced for the L1 probes by 20%, shifting from 130.0 to 103.5 μm with the coating. Microglia as far as 270 μm from the implant site displayed significantly lower morphological characteristics of activation for the L1 group. These results suggest that the L1 surface treatment works in an acute setting by microglial mediated mechanisms.
authors.affiliation: Bioengineering, University of Pittsburgh, United States; Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, United States.
authors.forename: James R
authors.initials: JR
authors.lastname: Eles
authors.affiliation: Bioengineering, University of Pittsburgh, United States; Radiology, University of Pittsburgh, United States; Neurobiology, University of Pittsburgh, United States.
authors.forename: Alberto L
authors.initials: AL
authors.lastname: Vazquez
authors.affiliation: Bioengineering, University of Pittsburgh, United States; Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, United States.
authors.forename: Noah R
authors.initials: NR
authors.lastname: Snyder
authors.affiliation: Neurobiology, University of Pittsburgh, United States.
authors.forename: Carl
authors.initials: C
authors.lastname: Lagenaur
authors.affiliation: Radiology, University of Pittsburgh, United States.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Murphy
authors.affiliation: Bioengineering, University of Pittsburgh, United States; Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, United States; McGowan Institute for Regenerative Medicine, University of Pittsburgh, United States; NeuroTech Center of the University of Pittsburgh Brain Institute, United States. Electronic address: tdk18@pitt.edu.
authors.forename: Takashi D Y
authors.initials: TD
authors.lastname: Kozai
authors.affiliation: Bioengineering, University of Pittsburgh, United States; Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, United States; McGowan Institute for Regenerative Medicine, University of Pittsburgh, United States. Electronic address: xic11@pitt.edu.
authors.forename: X Tracy
authors.initials: XT
authors.lastname: Cui
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D020099:Coated Materials, Biocompatible / Q000009:adverse effects / Q000737:chemistry*; D004567:Electrodes, Implanted / Q000009:adverse effects; D005549:Foreign-Body Reaction / Q000209:etiology / Q000517:prevention & control; D055767:Immobilized Proteins / Q000009:adverse effects / Q000737:chemistry*; D051379:Mice; D008822:Mice, Transgenic; D008839:Microelectrodes / Q000009:adverse effects; D017628:Microglia / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D039842:Neural Cell Adhesion Molecule L1 / Q000009:adverse effects / Q000737:chemistry*
chemical_list: D020099:Coated Materials, Biocompatible; D055767:Immobilized Proteins; D039842:Neural Cell Adhesion Molecule L1
keywords: Biomimetic coatings; Foreign body response; Microelectrode implants; Neural camouflage; Protein immobilization; Surface modification