Glial responses to implanted electrodes in the brain

Salatino, Joseph W.; Ludwig, Kip A.; Kozai, Takashi D. Y.; Purcell, Erin K.

doi:10.1038/s41551-017-0154-1

Cited by 644Neuroscience and Neural EngineeringNeuroinflammation and Neurodegeneration MechanismsVagus Nerve Stimulation Research

Glial responses to implanted electrodes in the brain

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Salatino, Joseph W., Ludwig, Kip A., Kozai, Takashi D. Y., Purcell, Erin K.·2017·Nature Biomedical Engineering

DOI 10.1038/s41551-017-0154-1PMC PMC6261524

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Abstract

The use of implants that can electrically stimulate or record electrophysiological or neurochemical activity in nervous tissue is rapidly expanding. Despite remarkable results in clinical studies and increasing market approvals, the mechanisms underlying the therapeutic effects of neuroprosthetic and neuromodulation devices, as well as their side effects and reasons for their failure, remain poorly understood. A major assumption has been that the signal-generating neurons are the only important target cells of neural-interface technologies. However, recent evidence indicates that the supporting glial cells remodel the structure and function of neuronal networks and are an effector of stimulation-based therapy. Here, we reframe the traditional view of glia as a passive barrier, and discuss their role as an active determinant of the outcomes of device implantation. We also discuss the implications that this has on the development of bioelectronic medical devices.

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The fibrotic capsule forming around an implant damages and displaces the target neuronal tissue.
“The fibrotic capsule forming around the implant not only damages and displaces the target neuronal tissue, but also forms a high-impedance layer that dampens the weak electrical signals produced by neurons and dissipates stimulating electrode currents.”
From Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics (2021) · cites this paper as Salatino et al., 2017
In “Astrocytic responses to device insertion” (page unavailable), the paper describes glial encapsulation around implanted electrodes and says the associated inflammatory response drives nearby neurons toward neurodegeneration. It does not say that the capsule physically displaces neuronal tissue, and it describes the capsule as glial rather than fibrotic. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Despite differences in cell types, the general principles underlying FBR and its consequences (fibrotic capsule formation, inflammatory damage to surrounding tissue) still apply in the CNS.
“Despite these differences, the general principles underlying FBR and the consequences (formation of a fibrotic capsule, inflammatory damage to the surrounding tissue) still apply (Polikov et al., 2005; Salatino et al., 2017).”
From Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics (2021) · cites this paper as Salatino et al., 2017
In “Astrocytic responses to device insertion” (page unavailable), the paper describes a foreign-body response in the brain involving glial encapsulation and inflammatory pathways that can drive nearby neurons toward neurodegeneration. It describes the encapsulating structure as reactive glia, however, rather than establishing that a fibrotic capsule forms in the CNS. (LLM, conf=0.84)
Experimental — accuracy not yet measured
The fibrotic capsule forms a high-impedance layer that dampens weak electrical signals produced by neurons and dissipates stimulating electrode currents.
“The fibrotic capsule forming around the implant not only damages and displaces the target neuronal tissue, but also forms a high-impedance layer that dampens the weak electrical signals produced by neurons and dissipates stimulating electrode currents.”
From Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics (2021) · cites this paper as Salatino et al., 2017
In “Extracellular recordings” (page unavailable), the paper says glial encapsulation may impede signal detection, but describes its effect on recording quality as ill-defined and notes that scarring may have little effect on signal amplitude. In “Neurostimulation” (page unavailable), it says increased impedance can reduce current reaching tissue under constant-voltage stimulation, whereas delivered charge under constant-current stimulation does not depend on those impedance changes. The claim presents these qualified effects as general properties of a fibrotic capsule. (LLM, conf=0.85)
Experimental — accuracy not yet measured
FBR is currently the key culprit behind chronically-implanted neuroprosthetic implant failure.
“FBR is currently the key culprit behind chronically-implanted neuroprosthetic implant failure (Polikov et al., 2005; Salatino et al., 2017), and poses a major hurdle to the clinical translation of new neuroprosthetic technologies.”
From Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics (2021) · cites this paper as Salatino et al., 2017
The Abstract (page unavailable) identifies poor biocompatibility and tissue integration as a significant limitation for implanted electrode arrays. The section ‘Astrocytic responses to device insertion’ describes the foreign-body response and its contribution to declining electrode performance. But the paper also identifies other biological and non-biological factors and does not establish the foreign-body response as the key cause of chronic implant failure. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Flexible implants in general show improved tissue compatibility compared to stiffer equivalents, minimizing trauma and FBR arising from shear damage.
“Flexible implants in general show improved tissue compatibility compared to stiffer equivalents, minimizing trauma and FBR arising from shear damage (Lacour et al., 2016; Salatino et al., 2017).”
From Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics (2021) · cites this paper as Salatino et al., 2017
The Biomaterials and glial activation section (page not supplied) says softer materials provoke less glial activation than stiff substrates and that reducing mechanical mismatch improves gliosis, inflammation and neuronal preservation. That supports improved tissue compatibility for flexible brain electrodes, but the paper does not establish the claim for implants in general or specifically attribute reduced trauma and foreign-body response to less shear damage. (LLM, conf=0.84)
Experimental — accuracy not yet measured

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Research works printed but not linked: 2

[66]Humphrey DR Schmidt EM Neurophysiological Techniques II Boulton AA Baker GB Vanderwolf CH 1 64 Humana Press New York 1990
[67]Shoham S Nagarajan S Neuroprosthetics: Theory and Practice 448 465 World Scientific 2003

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Authors: Salatino, J. W., Ludwig, K. A., Kozai, T. D. Y., & Purcell, E. K.
Affiliations: Michigan State University (US)
Mayo Clinic (US)
University of Pittsburgh (US)
Corresponding author: Purcell, Erin K.
ORCID: Salatino, Joseph W.
Ludwig, Kip A.
Kozai, Takashi D. Y.
Purcell, Erin K.
Venue: Nature Biomedical Engineering
Publisher: Springer Science and Business Media LLC
Published: 2017-11-10
Volume: 1
Issue: 11
Pages: 862-877
ISSN: 2157-846X (ISSN-L)
DOI: 10.1038/s41551-017-0154-1
PMC: PMC6261524
OpenAlex: W2765960015
Cited by: 642
References: 231
Citations by year: 2026: 77 · 2025: 110 · 2024: 92 · 2023: 95 · 2022: 68 · 2021: 76 · 2020: 61 · 2019: 38 · 2018: 24 · 2017: 1
FWCI: 16.46
Type: journal article
Language: en
Update notices: correction (2017-12-07)
Open access: green
europepmc.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Biomedical Engineering (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Grainger Foundation
National Institutes of Health
National Institute of Neurological Disorders and Stroke (R03NS095202, R21NS094900, R01NS094396)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Keywords: glial cells, implanted electrodes, neuroprosthetics, neuromodulation, neural interfaces, device implantation outcomes

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