Characterising epi-perineurial barrier function by microscale techniques including a miniaturised Ussing chamber Article Swipe
Susanne M. Krug
,
I M Lee
,
Lukas Knobe
,
Beate Hartmannsberger
,
Mena Atalla
,
Heike L. Rittner
,
Michael Fromm
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1016/j.actbio.2025.04.043
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1016/j.actbio.2025.04.043
Barriers of peripheral nerves, like the sciatic nerve, are complex structures, consisting of the inner endoneurial capillary barriers and the outer epi‑ and perineurial layers. The latter two, collectively also known as epi‑perineurium (EPN), are necessary for maintenance of the nerve homeostasis. However, the involvement of the EPN in altered nerve conduction in neuropathy is not well-understood. To date, reliable data on barrier properties and ion permeabilities have been limited by the difficulty of accessing the barrier experimentally. For analysing the EPN of rat sciatic nerves, we developed a preparation technique and a miniaturised (area 0.6 mm²), though edge damage-free, Ussing chamber. Electrophysiological characterisation included measurement of transepiperineurial resistance, differentiation of para- and transcellular contributions to this by two-path impedance spectroscopy and determination of permeabilities for flux markers and for ions by dilution and bi-ionic potential measurements.We found the EPN being definable as tight and responsive to changes in the gradients between the endoneurial and the extra-nerval compartment. In a rat model of bortezomib (Bortezomib)-induced polyneuropathy, we demonstrate the EPN to be impaired with a specific increase in potassium permeability, which normalises with the recovery of the animals.In conclusion, we present an advanced, dependable method to analyse the EPN, which can be extended to other microscale epi‑ or endothelia. Functionally, we demonstrate with this technique that the EPN forms a crucial and specific barrier to maintain ion gradients within the sciatic nerve. STATEMENT OF SIGNIFICANCE: We developed a miniaturized Ussing chamber allowing precise electrophysiological analysis of microscale barrier tissues, avoiding edge damage and experimental interferences. Using this, we characterized the epi‑perineurium (EPN) barrier of sciatic nerves, demonstrating it to be a tight and responsive barrier, essential for maintaining ion balance within that nerve. In a neuropathy model, we identified impaired potassium permeability during hyperalgesia, which normalized with recovery. Beyond the EPN, this method is broadly applicable to other previously inaccessible microscale barriers, enabling advanced studies of barrier (patho)physiology. Our work bridges biomaterial development and tissue barrier research, providing detailed insights into ion and solute transport, and may be used to study regulatory mechanisms and the subsequent development of potential therapeutic strategies such as targeted drug delivery across these barrier tissues.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.actbio.2025.04.043
- OA Status
- hybrid
- Cited By
- 1
- References
- 50
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4409662186
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4409662186Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1016/j.actbio.2025.04.043Digital Object Identifier
- Title
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Characterising epi-perineurial barrier function by microscale techniques including a miniaturised Ussing chamberWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-04-22Full publication date if available
- Authors
-
Susanne M. Krug, I M Lee, Lukas Knobe, Beate Hartmannsberger, Mena Atalla, Heike L. Rittner, Michael FrommList of authors in order
- Landing page
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https://doi.org/10.1016/j.actbio.2025.04.043Publisher landing page
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YesWhether a free full text is available
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hybridOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1016/j.actbio.2025.04.043Direct OA link when available
- Concepts
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Microscale chemistry, Ussing chamber, Materials science, Function (biology), Barrier function, Biomedical engineering, Nanotechnology, Medicine, Biology, Pathology, Epithelium, Cell biology, Mathematics, Mathematics educationTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
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2025: 1Per-year citation counts (last 5 years)
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50Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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