In vitro model of glial scarring around neuroelectrodes chronically implanted in the CNS

Vadim S. Polikov, Michelle L. Block, Jean Marc Fellous, Jau Shyong Hong, W. Monty Reichert

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

A novel in vitro model of glial scarring was developed by adapting a primary cell-based system previously used for studying neuroinflammatory processes in neurodegenerative disease. Midbrains from embryonic day 14 Fischer 344 rats were mechanically dissociated and grown on poly-d-lysine coated 24 well plates to a confluent layer of neurons, astrocytes, and microglia. The culture was injured with either a mechanical scrape or foreign-body placement (segments of 50 μm diameter stainless steel microwire), fixed at time points from 6 h to 10 days, and assessed by immunocytochemistry. Microglia invaded the scraped wound area at early time points and hypertrophied activated astrocytes repopulated the wound after 7 days. The chronic presence of microwire resulted in a glial scar forming at 10 days, with microglia forming an inner layer of cells coating the microwire, while astrocytes surrounded the microglial core with a network of cellular processes containing upregulated GFAP. Vimentin expressing cells and processes were present in the scrape at early times and within the astrocyte processes forming the glial scar. Neurons within the culture did not repopulate the scrape wound and did not respond to the microwire, although they were determined to be electrically active through patch clamp recording. The time course and relative positions of the glia in response to the different injury paradigms correlated well with stereotypical in vivo responses and warrant further work in the development of a functional in vitro test bed.

Original languageEnglish (US)
Pages (from-to)5368-5376
Number of pages9
JournalBiomaterials
Volume27
Issue number31
DOIs
StatePublished - Nov 1 2006
Externally publishedYes

Keywords

  • Biocompatibility
  • Brain
  • Cell culture
  • Foreign-body response
  • In vitro test
  • Neural prosthesis

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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