Skip to main content
SpringerLink
Log in

Effects of Glial Cells on Electrode Impedance Recorded from Neural Prosthetic Devices In Vitro

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Neural prosthetic devices hold the potential to be used in the treatment of a variety of neurological disorders. However, their long-term clinical success is currently limited by the ability to achieve stable interfaces between devices and the CNS. Immunohistochemical analysis has shown that cellular responses occur in tissue surrounding implanted devices. These cellular responses have been correlated with the impedance measured from device electrodes, leading to the hypothesis that a possible mechanism resulting in inconsistent device performance is the formation of an electrically insulating glial sheath at the implantation site. However, little is known about what cellular and tissue changes affect impedance values and thus contribute to the decreases in electrode performance. We have designed an in vitro system in which cell conditions can be varied within an artificial tissue matrix surrounding a neural prosthetic device. In this study, high-density cultures of glial cells were analyzed by immunohistochemical methods and impedance spectroscopy. Astrocytes and microglia were cultured at various ratios within the matrix surrounding the probes, and were observed over a period of 2 weeks. Cell seeding conditions and confocal images were compared to impedance data to enable the effects of glial cell type on electrode impedance to be determined.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  1. Andrade, D. M., et al. Long-term follow-up of patients with thalamic deep brain stimulation for epilepsy. Neurology 66(10):1571–1573, 2006.

    Article  PubMed  CAS  Google Scholar 

  2. Banker, G., and K. Goslin. Culturing Nerve Cells. Cambridge: MIT Press, 1998.

    Google Scholar 

  3. Bard, A. J., and L. R. Faulkner. Electrochemical Methods: Fundamentals and Applications. New York: John Wiley & Sons, 2001.

    Google Scholar 

  4. Biran, R., D. C. Martin, and P. A. Tresco. Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays. Exp. Neurol. 195(1):115–126, 2005.

    Article  PubMed  CAS  Google Scholar 

  5. Biran, R., D. C. Martin, and P. A. Tresco. 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):169–178, 2007.

    PubMed  Google Scholar 

  6. Bjornsson, C. S., et al. Effects of insertion conditions on tissue strain and vascular damage during neuroprosthetic device insertion. J. Neural Eng. 3(3):196–207, 2006.

    Article  PubMed  CAS  Google Scholar 

  7. Bjornsson, C. S., et al. Associative image analysis: a method for automated quantification of 3D multi-parameter images of brain tissue. J. Neurosci. Methods 170(1):165–178, 2008.

    Article  PubMed  Google Scholar 

  8. Butson, C. R., and C. C. McIntyre. Tissue and electrode capacitance reduce neural activation volumes during deep brain stimulation. Clin. Neurophysiol. 116(10):2490–2500, 2005.

    Article  PubMed  Google Scholar 

  9. Butson, C. R., et al. Patient-specific analysis of the volume of tissue activated during deep brain stimulation. Neuroimage 34(2):661–670, 2007.

    Article  PubMed  Google Scholar 

  10. Denes, A., et al. Proliferating resident microglia after focal cerebral ischaemia in mice. J. Cereb. Blood Flow Metab. 27(12):1941–1953, 2007.

    Article  PubMed  CAS  Google Scholar 

  11. Dhoot, N. O., et al. Peptide-modified alginate surfaces as a growth permissive substrate for neurite outgrowth. J. Biomed. Mater. Res. A 71(2):191–200, 2004.

    Article  PubMed  CAS  Google Scholar 

  12. Drury, J. L., R. G. Dennis, and D. J. Mooney. The tensile properties of alginate hydrogels. Biomaterials 25(16):3187–3199, 2004.

    Article  PubMed  CAS  Google Scholar 

  13. Dutcher, S. A., et al. Patterns of immediate early gene mRNA expression following rodent and human traumatic brain injury. Neurol. Res. 21(3):234–242, 1999.

    PubMed  CAS  Google Scholar 

  14. Eiselt, P., et al. Porous carriers for biomedical applications based on alginate hydrogels. Biomaterials 21(19):1921–1927, 2000.

    Article  PubMed  CAS  Google Scholar 

  15. Frampton, J. P., M. L. Shuler, M. R. Hynd, and W. Shain. Fabrication and optimization of alginate hydrogels for neural cell culture, 2009 (In Submission).

  16. Frampton, J. P., et al. Three-dimensional hydrogel cultures for modeling changes in tissue impedance around microfabricated neural probes. J. Neural Eng. 4(4):399–409, 2007.

    Article  PubMed  CAS  Google Scholar 

  17. Franks, W., et al. Impedance characterization and modeling of electrodes for biomedical applications. IEEE Trans. Biomed. Eng. 52(7):1295–1302, 2005.

    Article  PubMed  Google Scholar 

  18. Griffith, R. W., and D. R. Humphrey. Long-term gliosis around chronically implanted platinum electrodes in the Rhesus macaque motor cortex. Neurosci. Lett. 406(1–2):81–86, 2006.

    Article  PubMed  CAS  Google Scholar 

  19. Haynes, S. E., et al. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat. Neurosci. 9(12):1512–1519, 2006.

    Article  PubMed  CAS  Google Scholar 

  20. Kong, H. J., M. K. Smith, and D. J. Mooney. Designing alginate hydrogels to maintain viability of immobilized cells. Biomaterials 24(22):4023–4029, 2003.

    Article  PubMed  CAS  Google Scholar 

  21. Kong, H. J., et al. Controlling rigidity and degradation of alginate hydrogels via molecular weight distribution. Biomacromolecules 5(5):1720–1727, 2004.

    Article  PubMed  CAS  Google Scholar 

  22. Koshinaga, M., et al. Rapid microglial activation induced by traumatic brain injury is independent of blood brain barrier disruption. Histol. Histopathol. 22(2):129–135, 2007.

    PubMed  CAS  Google Scholar 

  23. Limousin, P., and I. Martinez-Torres. Deep brain stimulation for Parkinson’s disease. Neurotherapeutics 5(2):309–319, 2008.

    Article  PubMed  Google Scholar 

  24. Liu, X., et al. Stability of the interface between neural tissue and chronically implanted intracortical microelectrodes. IEEE Trans. Rehabil. Eng. 7(3):315–326, 1999.

    Article  PubMed  CAS  Google Scholar 

  25. Martin, D. L., and W. Shain. High affinity transport of taurine and beta-alanine and low affinity transport of gamma-aminobutyric acid by a single transport system in cultured glioma cells. J. Biol. Chem. 254(15):7076–7084, 1979.

    PubMed  CAS  Google Scholar 

  26. Merrill, D. R., and P. A. Tresco. Impedance characterization of microarray recording electrodes in vitro. IEEE Trans. Biomed. Eng. 52(11):1960–1965, 2005.

    Article  PubMed  Google Scholar 

  27. Normann, R. A. Technology insight: future neuroprosthetic therapies for disorders of the nervous system. Nat. Clin. Pract. Neurol. 3(8):444–452, 2007.

    Article  PubMed  Google Scholar 

  28. Polikov, V. S., P. A. Tresco, and W. M. Reichert. Response of brain tissue to chronically implanted neural electrodes. J. Neurosci. Methods 148(1):1–18, 2005.

    Article  PubMed  Google Scholar 

  29. Preston, E., J. Webster, and D. Small. Characteristics of sustained blood–brain barrier opening and tissue injury in a model for focal trauma in the rat. J. Neurotrauma 18(1):83–92, 2001.

    Article  PubMed  CAS  Google Scholar 

  30. Retterer, S. T., et al. Model neural prostheses with integrated microfluidics: a potential intervention strategy for controlling reactive cell and tissue responses. IEEE Trans. Biomed. Eng. 51(11):2063–2073, 2004.

    Article  PubMed  Google Scholar 

  31. Rowley, J. A., G. Madlambayan, and D. J. Mooney. Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials 20(1):45–53, 1999.

    Article  PubMed  CAS  Google Scholar 

  32. Schalk, G., et al. Two-dimensional movement control using electrocorticographic signals in humans. J. Neural Eng. 5(1):75–84, 2008.

    Article  PubMed  CAS  Google Scholar 

  33. Schiff, N. D., et al. Behavioural improvements with thalamic stimulation after severe traumatic brain injury. Nature 448(7153):600–603, 2007.

    Article  PubMed  CAS  Google Scholar 

  34. Schwab, J. M., K. Seid, and H. J. Schluesener. Traumatic brain injury induces prolonged accumulation of cyclooxygenase-1 expressing microglia/brain macrophages in rats. J. Neurotrauma 18(9):881–890, 2001.

    Article  PubMed  CAS  Google Scholar 

  35. Schwartz, A. B. Cortical neural prosthetics. Annu. Rev. Neurosci. 27:487–507, 2004.

    Article  PubMed  CAS  Google Scholar 

  36. Seymour, J. P., and D. R. Kipke. Neural probe design for reduced tissue encapsulation in CNS. Biomaterials 28(25):3594–3607, 2007.

    Article  PubMed  CAS  Google Scholar 

  37. Siddiqui, M. S., et al. Deep brain stimulation: treating neurological and psychiatric disorders by modulating brain activity. NeuroRehabilitation 23(1):105–113, 2008.

    PubMed  Google Scholar 

  38. Spataro, L., et al. Dexamethasone treatment reduces astroglia responses to inserted neuroprosthetic devices in rat neocortex. Exp. Neurol. 194(2):289–300, 2005.

    Article  PubMed  CAS  Google Scholar 

  39. Szarowski, D. H., et al. Brain responses to micro-machined silicon devices. Brain Res. 983(1–2):23–35, 2003.

    Article  PubMed  CAS  Google Scholar 

  40. Turner, J. N., et al. Cerebral astrocyte response to micromachined silicon implants. Exp. Neurol. 156(1):33–49, 1999.

    Article  PubMed  CAS  Google Scholar 

  41. Williams, J. C., et al. Complex impedance spectroscopy for monitoring tissue responses to inserted neural implants. J. Neural Eng. 4(4):410–423, 2007.

    Article  PubMed  Google Scholar 

  42. Winter, J. O., S. F. Cogan, and J. F. Rizzo, 3rd. Neurotrophin-eluting hydrogel coatings for neural stimulating electrodes. J. Biomed. Mater. Res. B Appl. Biomater 81(2):551–563, 2007.

    PubMed  Google Scholar 

  43. Wolpaw, J. R., and D. J. McFarland. Control of a two-dimensional movement signal by a noninvasive brain–computer interface in humans. Proc. Natl Acad. Sci. USA 101(51):17849–17854, 2004.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge the Wadsworth Center Advanced Light Microscopy and Image Analysis Core and its director, Richard Cole. This work was supported in part by the Nanobiotechnology Center (NBTC) an STC program of the NSF under agreement number ECS-9876771, by NIBIB (R21R21EB007782), and by NIH (NS R01-04488145).

Author information

Authors and Affiliations

  1. Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, NY, USA

    John P. Frampton & William Shain

  2. Wadsworth Center, New York State Department of Health, Albany, NY, USA

    Matthew R. Hynd & William Shain

  3. Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA

    Michael L. Shuler

  4. Biggs Laboratory, Empire State Plaza, Albany, NY, 12201, USA

    John P. Frampton

Authors
  1. John P. Frampton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew R. Hynd
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael L. Shuler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. William Shain
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John P. Frampton.

Additional information

Associate Editor John A. White oversaw the review of this article.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Figure 1

Alginate and Probe Setup. NeuroNexus probes/PCBs were mounted on glass frames. Teflon chambers were attached to the glass frames using PDMS, providing a well to contain cell culture medium. Diagrams illustrate the approximate position of the probe (containing electrodes) relative to the glass frame and the alginate matrix. Supplementary material 1 (TIFF 77520 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Frampton, J.P., Hynd, M.R., Shuler, M.L. et al. Effects of Glial Cells on Electrode Impedance Recorded from Neural Prosthetic Devices In Vitro . Ann Biomed Eng 38, 1031–1047 (2010). https://doi.org/10.1007/s10439-010-9911-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-010-9911-y

Keywords

Search

Navigation