Degeneration and regeneration in rabbit peripheral nerve with long-term nerve cuff electrode implant: A stereological study of myelinated and unmyelinated axons
Abstract
Selective and dynamically co-ordinated functional electrical stimulation (FES) of paralysed/paretic limbs in upper motor neuron lesioned people depends on optimal contact at the neural interface. Implanted nerve cuff electrodes may form a stable electrical neural interface, but may also inflict nerve damage. In this study the immediate and long-term effects of cuff implantation on the number and sizes of myelinated and unmyelinated axons have been evaluated with unbiased stereological techniques. Cuff electrodes were implanted in rabbit tibial nerves just below the knee joint, and the stereological analyses were carried out 2 weeks and 16 months after implantation. Myelinated axons were analysed at standardised levels proximal to, underneath, and distal to the cuff; unmyelinated axons underneath the cuff. A 27% loss of myelinated axons was found underneath and distal to the nerve cuff 2 weeks post surgery. All axonal sizes were equally lost except for the very smallest. At 16 months post surgery the number of myelinated axons was restored to control values at both levels. Except for the presence of regenerative sprouts at 2 weeks post surgery, no changes in the number or sizes of unmyelinated axons were revealed at either 2 weeks or 16 months post surgery. Our study demonstrates that implanted cuff electrodes may cause an initial loss of myelinated axons but with subsequent regeneration.
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Chronic implantation of snug cuffs modifies nerve shape and produces loss of large nerve fibers, which are the most sensitive to compression.
“Although snug-fitting nerve cuffs have been advocated to reduce the stimulus charge injection or to obtain a high signal-to-noise ratio for neural recordings (Naples et al., 1990) , different studies have shown that chronic implantation of snug cuffs modifies the nerve shape and produces a loss of large nerve fibers, which are the most sensitive to compression (Krarup et al., 1989; Grill and Mort”
From A critical review of interfaces with the peripheral nervous system for the control of neuroprostheses and hybrid bionic systems (2005) · cites this paper as Larsen et al., 1998
Neural damage induced by implantation and presence of an extraneural electrode is reversible.
“Girsch et al. and Larsen et al. showed that neural damage induced by the implantation and presence of an extraneural electrode is reversible [53, 54].”
From Safety of long-term electrical peripheral nerve stimulation: review of the state of the art (2019) · cites this paper as [54]
In rabbit tibial nerve, full regeneration occurred after an initial loss of 27% of myelinated axons following cuff electrode implantation.
“Larsen et al. evaluated axonal loss in the rabbit tibial nerve 2 weeks and 16 months after implantation of cuff electrodes, and demonstrated full regeneration after an initial loss of 27% of myelinated axons.”
From Safety of long-term electrical peripheral nerve stimulation: review of the state of the art (2019) · cites this paper as [54]
These damages could be reversible if no further stimulation is applied.
“These damages could be reversible if no further stimulation is applied [54, 113].”
From Safety of long-term electrical peripheral nerve stimulation: review of the state of the art (2019) · cites this paper as [54]
These drawbacks may induce irreversible damage to the nerves and cause serious biological issues, including inflammation, demyelination, axonal degradation, and blood vein compression.
“These drawbacks may induce irreversible damage to the nerves and cause serious biological issues, including inflammation, demyelination, axonal degradation, and blood vein compression (14–17).”
From Climbing-inspired twining electrodes using shape memory for peripheral nerve stimulation and recording (2019) · cites this paper as [16]
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Kameswaran, N. (2010) · ScholarlyCommons (University of Pennsylvania)
Historical Background from 1986 – 2005 for the Development of the ActiGait System
Haase, J., Haugland, M. K., & Sinkjær, T. (2014) · Biosystems & biorobotics · doi:10.1007/978-3-319-08072-7_61
Self-citationApplication of sensory nerve signals in neural prosthesis devices
Sinkjær, T. (1999) · VBN Forskningsportal (Aalborg Universitet)
Self-citationPeripheral Nerve Signal Processing, Multipole Cuff Methods
Yoo, P. (2015) · Encyclopedia of Computational Neuroscience · doi:10.1007/978-1-4614-6675-8_216
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Peripheral Nerve Signal Processing, Multipole Cuff Methods
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Peripheral Nerve Signal Processing, Multipole Cuff Methods
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Advancing Peripheral Nerve Interfaces in a Large Animal Model
Andreis, F. R. (2022) · doi:10.54337/aau478976327
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Zhao, Q., Liu, Q., Li, B., Yang, X., Yan, J., Zou, J., Zhang, R., Tian, G., Cui, M., Wang, Q., et al. (2026) · Advanced Materials · doi:10.1002/adma.73685
- Authors
- Larsen, J. O., Thomsen, M., Haugland, M., & Sinkjær, T.
- Affiliations
- Aalborg University Hospital (DK)
- Aalborg University (DK)
- Venue
- Acta Neuropathologica
- Published
- 1998-10-09
- Volume
- 96
- Issue
- 4
- Pages
- 365-378
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2024281494
- Cited by
- 96
- References
- 12
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 6 · 2016: 1 · 2015: 7 · 2014: 6 · 2013: 2 · 2012: 2
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Keywords
- cuff electrodes, peripheral nerve injury, axonal loss, axon regeneration, myelinated axons, unmyelinated axons, axon diameter, functional electrical stimulation, neural interfaces, tibial nerve, rabbit model
- MeSH terms
- Anatomy, Artistic, Animals, Axons, Electric Stimulation, Electrodes, Implanted, Female, Nerve Degeneration, Nerve Fibers, Nerve Fibers, Myelinated, Nerve Regeneration, Peripheral Nerves, Rabbits, Time Factors
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