PMID-23428842 Chronic intracortical microelectrode arrays induce non-uniform, depth-related tissue responses.
- Woolley AJ, Desai HA, Otto KJ.
- One timepoint, 4 weeks.
- Laser confocal microscopy
- after tissue clearing (optical index of refraction matching) in a 60% sucrose solution.
- Single-shank iridium contact silicon substrate MEA.
- Device cut level with surface of brain after insertion.
- Intact MEAs via device-capture histology, DHhist (Woolley et al 2011)
- 350-450um tissue explanted with device.
- They promote their technique.
- Tissue surrounding microdevices exhibited two major depth-related phenomena:
- a non-uniform microglial coating along the device length and
- a dense mass of cells surrounding the implant in cerebral cortical layers I and II.
- The dense mass of cells contained vimentin, a protein not typically expressed highly in CNS cells, evidence that non-CNS cells likely descended down the face of the penetrating devices from the pial surface.
- But no Iba1 (activated microglia) per se in the tissue mass.
-
- Hoe342 -- cell marker.
- This mass was apparently consistent across animals!
- Cells in the mass were VIM positive -- fibroblasts -- meninges?
- low GFAP = not an astrocytic scar.
- This study provides further evidence that a progressive invasion of non-CNS cells contributes substantially to the chronic phase of the tissue response around intracortical MEAs.
- Again, might be from BBB distruption {1237}
This result is supported by previous papers:
- {1193} -- microglia response not correlated to electrode failure, but correlated to ferritin immunoresponse
- {781} -- also note that menigeal fibroblasts migrate down electrode tracts.
- {1028} -- measured vimentin, GFAP, and ED1 (not Iba1). Found Vim+ and GFAP+, suggesting reactive astrocytes and not meningeal cells. ED1 aka CD68 is specific to macrophages and not microglia, so these may be blood-derived cells.
- {1200} -- chronic contact with the meninges v.s intraparenchymal correlated with Vim+ encapsulation.
- {1210} -- old paper showing the same result near surface of implant.
- {1196} -- more against GFAP & pro BBB disruption
- {1204} -- GFAP uncorrelated (!) with NeuN intensity
- {307} -- all initial tests of utah arrays showed fibrous encapsulation; one array was completely explanted. This is why now they put gore-tex over the implant -- to prevent fibroblast migration (i guess).
|