Glial Responses to Implanted Electrodes in the Brain

Overview

Journal Nat Biomed Eng

Publisher Springer Nature

Specialty Biomedical Engineering

Date 2018 Dec 4

PMID 30505625

Citations 207

Authors

Joseph W Salatino

Kip A Ludwig

Takashi D Y Kozai

Erin K Purcell

Affiliations

Soon will be listed here.

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.

Citing Articles

A Compact Low-Power Chopper Low Noise Amplifier for High Density Neural Front-Ends.

Fava A, Centurelli F, Monsurro P, Scotti G Sensors (Basel). 2025; 25(4).

PMID: 40006386 PMC: 11859806. DOI: 10.3390/s25041157.

Dexamethasone-loaded platelet-inspired nanoparticles improve intracortical microelectrode recording performance.

Shoffstall A, Li L, Hartzler A, Menendez-Lustri D, Zhang J, Chen A Res Sq. 2025; .

PMID: 39989959 PMC: 11844648. DOI: 10.21203/rs.3.rs-6018202/v1.

Bio-inspired electronics: Soft, biohybrid, and "living" neural interfaces.

Boufidis D, Garg R, Angelopoulos E, Cullen D, Vitale F Nat Commun. 2025; 16(1):1861.

PMID: 39984447 PMC: 11845577. DOI: 10.1038/s41467-025-57016-0.

A method for efficient, rapid, and minimally invasive implantation of individual non-functional motes with penetrating subcellular-diameter carbon fiber electrodes into rat cortex.

Letner J, Lam J, Copenhaver M, Barrow M, Patel P, Richie J bioRxiv. 2025; .

PMID: 39974888 PMC: 11838573. DOI: 10.1101/2025.02.05.636655.

Multifunctional hydrogel electronics for closed-loop antiepileptic treatment.

Qu J, Xie K, Chen S, He X, Wang Y, Chamberlin M Sci Adv. 2024; 10(47):eadq9207.

PMID: 39576849 PMC: 11584000. DOI: 10.1126/sciadv.adq9207.

References

Merrill D, Bikson M, Jefferys J . Electrical stimulation of excitable tissue: design of efficacious and safe protocols. J Neurosci Methods. 2005; 141(2):171-98. DOI: 10.1016/j.jneumeth.2004.10.020. View

Kolarcik C, Luebben S, Sapp S, Hanner J, Snyder N, Kozai T . Elastomeric and soft conducting microwires for implantable neural interfaces. Soft Matter. 2015; 11(24):4847-61. PMC: 4466039. DOI: 10.1039/c5sm00174a. View

Kerchner G, Nicoll R . Silent synapses and the emergence of a postsynaptic mechanism for LTP. Nat Rev Neurosci. 2008; 9(11):813-25. PMC: 2819160. DOI: 10.1038/nrn2501. View

Wadhwa R, Lagenaur C, Cui X . Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode. J Control Release. 2005; 110(3):531-41. DOI: 10.1016/j.jconrel.2005.10.027. View

Henry C, Huang Y, Wynne A, Godbout J . Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1beta and anti-inflammatory IL-10 cytokines. Brain Behav Immun. 2008; 23(3):309-17. PMC: 2692986. DOI: 10.1016/j.bbi.2008.09.002. View

Kozai T, Eles J, Vazquez A, Cui X . Two-photon imaging of chronically implanted neural electrodes: Sealing methods and new insights. J Neurosci Methods. 2015; 258:46-55. PMC: 4771525. DOI: 10.1016/j.jneumeth.2015.10.007. View

Li X, Chen W, Sheng J, Cao D, Wang W . Interleukin-6 inhibits voltage-gated sodium channel activity of cultured rat spinal cord neurons. Acta Neuropsychiatr. 2014; 26(3):170-7. DOI: 10.1017/neu.2013.49. View

Prasad A, Sanchez J . Quantifying long-term microelectrode array functionality using chronic in vivo impedance testing. J Neural Eng. 2012; 9(2):026028. DOI: 10.1088/1741-2560/9/2/026028. View

Chang S, Kim I, Marsh M, Jang D, Hwang S, Van Gompel J . Wireless fast-scan cyclic voltammetry to monitor adenosine in patients with essential tremor during deep brain stimulation. Mayo Clin Proc. 2012; 87(8):760-5. PMC: 3538486. DOI: 10.1016/j.mayocp.2012.05.006. View

10.

Jiang J, Willett F, Taylor D . Relationship between microelectrode array impedance and chronic recording quality of single units and local field potentials. Annu Int Conf IEEE Eng Med Biol Soc. 2015; 2014:3045-8. DOI: 10.1109/EMBC.2014.6944265. View

11.

Sun D, Yu H, Spooner J, Tatsas A, Davis T, Abel T . Postmortem analysis following 71 months of deep brain stimulation of the subthalamic nucleus for Parkinson disease. J Neurosurg. 2008; 109(2):325-9. DOI: 10.3171/JNS/2008/109/8/0325. View

12.

McCreery D, Cogan S, Kane S, Pikov V . Correlations between histology and neuronal activity recorded by microelectrodes implanted chronically in the cerebral cortex. J Neural Eng. 2016; 13(3):036012. PMC: 7479968. DOI: 10.1088/1741-2560/13/3/036012. View

13.

Khakh B, Sofroniew M . Diversity of astrocyte functions and phenotypes in neural circuits. Nat Neurosci. 2015; 18(7):942-52. PMC: 5258184. DOI: 10.1038/nn.4043. View

14.

Agulhon C, Fiacco T, McCarthy K . Hippocampal short- and long-term plasticity are not modulated by astrocyte Ca2+ signaling. Science. 2010; 327(5970):1250-4. DOI: 10.1126/science.1184821. View

15.

Tawfik V, Chang S, Hitti F, Roberts D, Leiter J, Jovanovic S . Deep brain stimulation results in local glutamate and adenosine release: investigation into the role of astrocytes. Neurosurgery. 2010; 67(2):367-75. PMC: 2919357. DOI: 10.1227/01.NEU.0000371988.73620.4C. View

16.

Sasaki T, Beppu K, Tanaka K, Fukazawa Y, Shigemoto R, Matsui K . Application of an optogenetic byway for perturbing neuronal activity via glial photostimulation. Proc Natl Acad Sci U S A. 2012; 109(50):20720-5. PMC: 3528589. DOI: 10.1073/pnas.1213458109. View

17.

Rivers L, Young K, Rizzi M, Jamen F, Psachoulia K, Wade A . PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice. Nat Neurosci. 2008; 11(12):1392-401. PMC: 3842596. DOI: 10.1038/nn.2220. View

18.

Ludwig K, Langhals N, Joseph M, Richardson-Burns S, Hendricks J, Kipke D . Poly(3,4-ethylenedioxythiophene) (PEDOT) polymer coatings facilitate smaller neural recording electrodes. J Neural Eng. 2011; 8(1):014001. PMC: 3415981. DOI: 10.1088/1741-2560/8/1/014001. View

19.

Kozai T, Vazquez A, Weaver C, Kim S, Cui X . In vivo two-photon microscopy reveals immediate microglial reaction to implantation of microelectrode through extension of processes. J Neural Eng. 2012; 9(6):066001. PMC: 3511663. DOI: 10.1088/1741-2560/9/6/066001. View

20.

Ware T, Simon D, Liu C, Musa T, Vasudevan S, Sloan A . Thiol-ene/acrylate substrates for softening intracortical electrodes. J Biomed Mater Res B Appl Biomater. 2013; 102(1):1-11. DOI: 10.1002/jbmb.32946. View