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ref: -0 tags: winslow Tresco 2010 BBB histology immune response microelectrodes date: 04-19-2013 23:25 gmt revision:0 [head]

PMID-19963267 Quantitative analysis of the tissue response to chronically implanted microwire electrodes in rat cortex.

  • Winslow BD, Tresco PA.
  • The spatial distribution of biomarkers associated with the foreign body response to insulated microwires placed in rat cerebral cortex was analyzed 2, 4, and 12 weeks after implantation using quantitative methods.
  • We found no evidence that reactive gliosis increases over time or that neuronal loss is progressive, we did find evidence of persistent inflammation and enhanced BBB permeability at the electrode brain tissue interface that extended over the 3 month indwelling period and that exhibited more animal to animal variability at 3 months than at 2 and 4 weeks.

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ref: Polikov-2005.1 tags: neural response glia histology immune electrodes recording 2005 Tresco Michigan microglia date: 01-29-2013 00:34 gmt revision:10 [9] [8] [7] [6] [5] [4] [head]

PMID-16198003[0] Response of brain tissue to chronically implanted neural electrodes

  • Good review (the kind where figures are taken from other papers). Nothing terribly new (upon a very cursory inspection)
  • When CNS damage severs blood vessels, microglia are indistinguishable from the blood borne, monocyte-derived macrophages that are recruited by the degranulation of platelets and the cellular release of cytokines.
  • Furthermore, microglia are known to secrete, either constitutively, or in response to pathological stimuli, neurotrophic factors that aid in neuronal survival and growth.
    • Also release cytotoxic and neurotoxic factors that can lead to neuronal death in vitro.
    • It has been suggested that the presence of insoluble materials in the brain may lead to a state of 'frustrated phagocytosis' or inability of the macrophages to remove the foreign body, resulting in persistent release of neurotoxic substances.
  • When a 10x10 array of silicon probes was implanted in feline cortex, 60% of the needle tracks showed evidence of hemorrhage and 25% showed edema upon explantation of the probes after one day (Schmidt et al 1993) {1163}
    • Although a large number of the tracks were affected, only 3-5% of the area was actually covered by hemorrhages and edema, suggesting the actual damage to blood vessels may have been relatively minor. (!!)
  • Excess fluid and cellular debris diminishes 6-8 days due to the action of activated microglia and re-absorption.
  • As testament to the transitory nature of this mechanically induced wound healing response, electrode tracks could not be found in animals after several months when the electrode was inerted and quickly removed (Yuen and Agnew 1995, Rousche et al 2001; Csicsvari et al 2003, Biran et al 2005).
  • Biran et al 2005: observed persistent ED-1 immunoreactivity around silicon microelectrode arrays implanted in rat cortex at 2 and 4 weeks following implantation; not seen in microelectrode stab wound controls.
  • On the glial scar:
    • observed in the CNS of all vertebrates, presumably to isolate damaged parts of the nervous system and maintain the integrity of the blood-brain barrier.
    • mostly composed of reactive astrocytes.
    • presumably the glial scar insulates electrodes from nearby neurons, hindering diffusion and increasing impedance.
  • On the meninges:
    • Meningeal fibroblasts, which also stain for vimentin, but not for GFAP, may migrate down the electrode shaft from the brain surface and form the early basis for the glial scar.
  • On recording quality:
    • Histological examination upon explantation revealed that every electrode with stable unit recordings had at least one large neuron near the electrode tip, while every electrode that was not able to record resolvable action potentials was explanted from a site with no large neurons nearby.
  • Perhaps the clearest example of this variability was observed in the in vivo response to plastic “mock electrodes” implanted in rabbit brain by Stensaas and Stensaas (1976) {1210} and explanted over the course of 2 years. They separated the response into three types: Type 1 was characterized by little to no gliosis with neurons adjacent to the implant, Type 2 had a reactive astrocyte zone, and Type 3 exhibited a layer of connective tissue between the reactive astrocyte layer and the implant, with neurons pushed more than 100 um away. All three responses are well documented in the literature; however this study found that the model electrodes produced all three types of reactions simultaneously,depending on where along the electrode one looked.

____References____

[0] Polikov VS, Tresco PA, Reichert WM, Response of brain tissue to chronically implanted neural electrodes.J Neurosci Methods 148:1, 1-18 (2005 Oct 15)

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ref: Leung-2008.08 tags: biocompatibility alginate tissue response immunochemistry microglia insulation spin coating Tresco recording histology MEA date: 01-28-2013 21:19 gmt revision:4 [3] [2] [1] [0] [head]

PMID-18485471[0] Characterization of microglial attachment and cytokine release on biomaterials of differing surface chemistry

  • The important result is that materials with low protein-binding (e.g. alginate) have fewer bound microglia, hence better biocompatibility. It also seems to help if the material is highly hydrophilic.
    • Yes alginate is made from algae.
  • Used Michigan probes for implantation.
  • ED1 = pan-macrophage marker.
    • (quote:) Quantification of cells on the surface indicated that the number of adherent microglia appeared higher on the smooth side of the electrode compared to the grooved, recording site side (Fig. 2B), and declined with time. However, at no point were electrodes completely free of attached and activated microglial cells nor did these cells disappear from the interfacial zone along the electrode tract.
    • but these were not coated with anything new .. ???

____References____

[0] Leung BK, Biran R, Underwood CJ, Tresco PA, Characterization of microglial attachment and cytokine release on biomaterials of differing surface chemistry.Biomaterials 29:23, 3289-97 (2008 Aug)

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ref: Kim-2004.05 tags: histology electrode immune response Tresco hollow fiber membranes GFAP vimentin ED1 date: 01-28-2013 03:08 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-14741588[0] Chronic response of adult rat brain tissue to implants anchored to the skull.

  • The increase in tissue reactivity observed with transcranially implanted HFMs may be influenced by several mechanisms including chronic contact with the meninges and possibly motion of the device within brain tissue.
  • Broadly speaking, our results suggest that any biomaterial, biosensor or device that is anchored to the skull and in chronic contact with meningeal tissue will have a higher level of tissue reactivity than the same material completely implanted within brain tissue.
  • See also [1]
  • Could slice through the hollow fiber membrane for histology. (as we shall).
  • Good list of references.

____References____

[0] Kim YT, Hitchcock RW, Bridge MJ, Tresco PA, Chronic response of adult rat brain tissue to implants anchored to the skull.Biomaterials 25:12, 2229-37 (2004 May)
[1] Biran R, Martin DC, Tresco PA, The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull.J Biomed Mater Res A 82:1, 169-78 (2007 Jul)

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ref: Skousen-2011.01 tags: electrodes immune response Tresco Wise Michigan histology GFAP atrocyte surface area foreign body response date: 01-25-2013 01:44 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-21867802[0] Reducing surface area while maintaining implant penetrating profile lowers the brain foreign body response to chronically implanted planar silicon microelectrode arrays.

  • We studied the chronic brain foreign body response to planar solid silicon microelectrode arrays and planar lattice arrays with identical penetrating profiles but with reduced surface area in rats after an 8-week indwelling period.
  • Using quantitative immunohistochemistry, we found that presenting less surface area after equivalent iatrogenic injury is accompanied by significantly less
    • persistent macrophage activation,
    • decreased blood brain barrier leakiness,
    • and reduced neuronal cell loss.
  • Could be a factor of micromotion, too -- the lattice array has more anchoring points (?)
  • They propose it's a factor of TNF- α\alpha concentration around the implants. This, and other proinflammatory and cytoxic cytokines, is released by macrophages.
  • "Recent studies from our lab have described disruption of BBB integrity, indicated by the presence of autologous IgG in the brain parenchyma, surrounding both microwire and planar silicon recording devices ([1][2]. Under normal conditions, autologous IgG is excluded from the brain parenchyma (Azzi et al., 1990; Seitz et al., 1985) but has been observed following BBB disruption (Aihara et al., 1994).
    • E.g. the presence of IgG proves that the BBB was compromised.
      • Less so with the lattice implants.
  • Previous work from our lab using single microwires and single shaft, planar silicon microelectrode arrays indicated that the spatial distribution of GFAP does not increase with time over the indwelling period and did not support the “increase in astrogliosis over time hypothesis” as a dominant or general biologically related failure mechanism for this type of microelectrode recording device {1197}.

____References____

[0] Skousen JL, Merriam SM, Srivannavit O, Perlin G, Wise KD, Tresco PA, Reducing surface area while maintaining implant penetrating profile lowers the brain foreign body response to chronically implanted planar silicon microelectrode arrays.Prog Brain Res 194no Issue 167-80 (2011)
[1] Winslow BD, Christensen MB, Yang WK, Solzbacher F, Tresco PA, A comparison of the tissue response to chronically implanted Parylene-C-coated and uncoated planar silicon microelectrode arrays in rat cortex.Biomaterials 31:35, 9163-72 (2010 Dec)
[2] Winslow BD, Tresco PA, Quantitative analysis of the tissue response to chronically implanted microwire electrodes in rat cortex.Biomaterials 31:7, 1558-67 (2010 Mar)

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ref: Biran-2007.07 tags: tresco biocompatibility tether skull electrodes Michigan probe recording Tresco date: 01-24-2013 20:11 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-17266019[0] The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull.

  • Good, convincing, figures.

____References____

[0] Biran R, Martin DC, Tresco PA, The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull.J Biomed Mater Res A 82:1, 169-78 (2007 Jul)

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ref: Biran-2005.09 tags: Tresco histology chronic implantation astrocytes microglia date: 01-04-2013 02:28 gmt revision:3 [2] [1] [0] [head]

PMID-16045910[0] Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.

  • We observed persistent ED1 immunoreactivity around implanted silicon microelectrode arrays implanted in adult rat cortex that was accompanied by a significant reduction in nerve fiber density and nerve cell bodies in the tissue immediately surrounding the implanted silicon microelectrode arrays.
  • We found that explanted electrodes were covered with ED1/MAC-1 immunoreactive cells and that the cells released MCP-1 and TNF-a under serum-free conditions in vitro.
  • See also [1] and [2]
  • Electrodes: Michigan type, 5mm long, 200um wide tapering to 30um, 15um thick at the shank tapering to 2um.
    • Show that the chronic response is markedly different than acute stab wounds.
    • "Stab wounds resulted in comparatively minimal neurofilament loss at 2 weeks (A) and no apparent loss by 4 weeks".
    • "The number of neuronal bodies is reduced in the area adjacent to microelectrodes (B, D) but appears unaltered surrounding stab wound lesions (A, C; lesion site in center of each image)."
  • Includes details of immunostaining, which could be useful.

____References____

[0] Biran R, Martin DC, Tresco PA, Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.Exp Neurol 195:1, 115-26 (2005 Sep)
[1] Szarowski DH, Andersen MD, Retterer S, Spence AJ, Isaacson M, Craighead HG, Turner JN, Shain W, Brain responses to micro-machined silicon devices.Brain Res 983:1-2, 23-35 (2003 Sep 5)
[2] Gilletti A, Muthuswamy J, Brain micromotion around implants in the rodent somatosensory cortex.J Neural Eng 3:3, 189-95 (2006 Sep)