Targeting CD14 on blood derived cells improves intracortical microelectrode performance

Biomaterials. 2018 May;163:163-173. doi: 10.1016/j.biomaterials.2018.02.014. Epub 2018 Feb 13.

Abstract

Intracortical microelectrodes afford researchers an effective tool to precisely monitor neural spiking activity. Additionally, intracortical microelectrodes have the ability to return function to individuals with paralysis as part of a brain computer interface. Unfortunately, the neural signals recorded by these electrodes degrade over time. Many strategies which target the biological and/or materials mediating failure modes of this decline of function are currently under investigation. The goal of this study is to identify a precise cellular target for future intervention to sustain chronic intracortical microelectrode performance. Previous work from our lab has indicated that the Cluster of Differentiation 14/Toll-like receptor pathway (CD14/TLR) is a viable target to improve chronic laminar, silicon intracortical microelectrode recordings. Here, we use a mouse bone marrow chimera model to selectively knockout CD14, an innate immune receptor, from either brain resident microglia or blood-derived macrophages, in order to understand the most effective targets for future therapeutic options. Using single-unit recordings we demonstrate that inhibiting CD14 from the blood-derived macrophages improves recording quality over the 16 week long study. We conclude that targeting CD14 in blood-derived cells should be part of the strategy to improve the performance of intracortical microelectrodes, and that the daunting task of delivering therapeutics across the blood-brain barrier may not be needed to increase intracortical microelectrode performance.

Keywords: CD14; Electrophysiology; Gliosis; Innate immunity; Intracortical microelectrodes; Neuroinflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Blood Cells / metabolism*
  • Brain / cytology
  • Brain / metabolism
  • Brain-Computer Interfaces
  • Chimera
  • Electric Impedance
  • Electrodes, Implanted*
  • Female
  • Humans
  • Lipopolysaccharide Receptors / antagonists & inhibitors
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharide Receptors / metabolism*
  • Macrophages / metabolism
  • Male
  • Mice, Inbred C57BL
  • Microelectrodes*
  • Microglia / physiology
  • Neurons / metabolism
  • Silicon / chemistry

Substances

  • Lipopolysaccharide Receptors
  • Silicon