2. Academic Validation
  3. Inhibition of the cluster of differentiation 14 innate immunity pathway with IAXO-101 improves chronic microelectrode performance

Inhibition of the cluster of differentiation 14 innate immunity pathway with IAXO-101 improves chronic microelectrode performance

  • J Neural Eng. 2018 Apr;15(2):025002. doi: 10.1088/1741-2552/aaa03e.
John K Hermann 1 2,  Madhumitha Ravikumar 1 2,  Andrew J Shoffstall 1 2,  Evon S Ereifej 1 2,  Kyle M Kovach 1 2,  Jeremy Chang 1 2,  Arielle Soffer 1 2,  Chun Wong 1 2,  A Ali 1 2,  Patrick Smith 2,  Grace Protasiewicz 2,  Jingle Jiang 2,  Stephen M Selkirk 1 3 4,  Robert H Miller 5,  Steven Sidik 6,  Nicholas P Ziats 2 7,  Dawn M Taylor 2 8 9,  Jeffrey R Capadona 1 2
Affiliations

Affiliations

  • 1 Advanced Platform Technology Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Rehabilitation Research and Development, 10701 East Blvd. Mail Stop 151 AW/APT, Cleveland OH 44106, United States of America.
  • 2 Department of Biomedical Engineering, Case Western Reserve University, School of Engineering, 2071 Martin Luther King Jr Drive, Wickenden Bldg, Cleveland OH 44106, United States of America.
  • 3 Department of Neurology, Case Western Reserve University, School of Medicine, 11100 Euclid Avenue, Sears Tower Bldg, Cleveland OH 44106, United States of America.
  • 4 Spinal Cord Injury Division, Louis Stokes Cleveland Veterans Affairs Medical Center, 10701 East Blvd. Mail Stop 151 AW/APT, Cleveland OH 44106, United States of America.
  • 5 Neurosciences, The George Washington University, The School of Medicine and Health Sciences, 2300 Eye Street, NW, Ross Hall, Washington DC 20037, United States of America.
  • 6 Department of Mathematics, Applied Mathematics and Statistics, Case Western Reserve University, 2049 Martin Luther King Jr Drive, Yost Hall, Cleveland OH 44106, United States of America.
  • 7 Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Wolstein Research Bldg., Cleveland, OH 44106, United States of America.
  • 8 Department of Neurosciences, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland OH 44195, United States of America.
  • 9 Cleveland Functional Electrical Stimulation Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Rehabilitation Research and Development, 10701 EAST Blvd, Cleveland OH 44106, United States of America.
PMID: 29219114 DOI: 10.1088/1741-2552/aaa03e
Abstract

Objective: Neuroinflammatory mechanisms are hypothesized to contribute to intracortical microelectrode failures. The cluster of differentiation 14 (CD14) molecule is an innate immunity receptor involved in the recognition of pathogens and tissue damage to promote inflammation. The goal of the study was to investigate the effect of CD14 inhibition on intracortical microelectrode recording performance and tissue integration.

Approach: Mice implanted with intracortical microelectrodes in the motor cortex underwent electrophysiological characterization for 16 weeks, followed by endpoint histology. Three conditions were examined: (1) wildtype control mice, (2) knockout mice lacking CD14, and (3) wildtype control mice administered a small molecule inhibitor to CD14 called IAXO-101.

Main results: The CD14 knockout mice exhibited acute but not chronic improvements in intracortical microelectrode performance without significant differences in endpoint histology. Mice receiving IAXO-101 exhibited significant improvements in recording performance over the entire 16 week duration without significant differences in endpoint histology.

Significance: Full removal of CD14 is beneficial at acute time ranges, but limited CD14 signaling is beneficial at chronic time ranges. Innate immunity receptor inhibition strategies have the potential to improve long-term intracortical microelectrode performance.

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