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ref: Prasad-2012.1 tags: tungsten microwire electrodes histology insulation failure sanchez microwire tungsten date: 06-27-2013 22:40 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

PMID-23010756[0] Comprehensive characterization and failure modes of tungsten microwire arrays in chronic neural implants.

  • c.f. [1]
  • microwire implant, durations that ranged from acute to up to 9 months in 25 rats.
  • First 2-3 weeks electrode impedance + recording quality fluctuated the most widely.
  • Electrode recording site deterioration continued for the long-term animals as insulation damage occurred and recording surface became more recessed over time.
  • Activated microglia were found near electrode tracts in all chronic animals.
    • High ferritin expression, intraparenchymal bleeding, microglial degeneration suggesting presence of excessive oxidative stress via Fenton chemistry.
      • Wikipedia: Free iron is toxic to cells as it acts as a catalyst in the formation of free radicals from reactive oxygen species via the Fenton Reaction.[11] Hence vertebrates use an elaborate set of protective mechanisms to bind iron in various tissue compartments.
  • Ferritin expression sometimes associated with blebbing / cytorrhexis. (in figures 7-8)
    • Interestingly, during the first few hours after implantation many microglial cells are undergoing cytoplasmic fragmentation (cytorrhexis) which indicates ongoing degeneration of these cells as their cytoplasm literally breaks apart. Cytorrhexis has been previously observed in the aged human brain where it becomes particular prominent in subjects with Alzheimer’s disease.
  • Could not discriminate abiotic (insulation, recording site size) and biotic (inflammatory response) causes of failure.
    • Microglial response not correlated with prolonged performance.
  • Tungsten TDT microwire arrays. 50um diameter, 10um polyimide insulation.
  • SEM imaging pre and prior implantation.
  • Antibodies marking microglia:
    • Iba1 marks all microglia.
    • ED1 stain against CD68 to identify active macrophages [80], but not necessarily all activated microglia since many activated cells are not engaged in phagocytosis and thus are ED1-negative.
    • Anti-ferritin staining to identify those microglia involved in the sequestration of free iron that may leak as a result of BBB compromize.
      • Issue: ferritin is expressed in all tissues ..
    • OX-6 to identify antigen-presenting MHC-II (immune) cells, e.g. microglia or blood-borne immune cells.
  • Found the immunohistoheamistry not terribly convincing.
    • Above, arrows show withdrawn electrode tips.
  • Working with the FDA to promote good laboratory practice (GLP) and good manufacturing practice (GMP). Can mention the same.
  • No evidence of infection in rats.
    • Not true in monkeys..

____References____

[0] Prasad A, Xue QS, Sankar V, Nishida T, Shaw G, Streit WJ, Sanchez JC, Comprehensive characterization and failure modes of tungsten microwire arrays in chronic neural implants.J Neural Eng 9:5, 056015 (2012 Oct)
[1] Freire MA, Morya E, Faber J, Santos JR, Guimaraes JS, Lemos NA, Sameshima K, Pereira A, Ribeiro S, Nicolelis MA, Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants.PLoS One 6:11, e27554 (2011)