Malong, Liza;
Napoli, Ilaria;
Casal, Giulia;
White, Ian J;
Stierli, Salome;
Vaughan, Andrew;
Cattin, Anne-Laure;
... Lloyd, Alison C; + view all
(2023)
Characterization of the structure and control of the blood-nerve barrier identifies avenues for therapeutic delivery.
Developmental Cell
, 58
(3)
174-191.e8.
10.1016/j.devcel.2023.01.002.
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Abstract
The blood barriers of the nervous system protect neural environments but can hinder therapeutic accessibility. The blood-brain barrier (BBB) is well characterized, consisting of endothelial cells with specialized tight junctions and low levels of transcytosis, properties conferred by contacting pericytes and astrocytes. In contrast, the blood-nerve barrier (BNB) of the peripheral nervous system is poorly defined. Here, we characterize the structure of the mammalian BNB, identify the processes that confer barrier function, and demonstrate how the barrier can be opened in response to injury. The homeostatic BNB is leakier than the BBB, which we show is due to higher levels of transcytosis. However, the barrier is reinforced by macrophages that specifically engulf leaked materials, identifying a role for resident macrophages as an important component of the BNB. Finally, we demonstrate the exploitation of these processes to effectively deliver RNA-targeting therapeutics to peripheral nerves, indicating new treatment approaches for nervous system pathologies.
| Type: | Article |
|---|---|
| Title: | Characterization of the structure and control of the blood-nerve barrier identifies avenues for therapeutic delivery |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.devcel.2023.01.002 |
| Publisher version: | https://doi.org/10.1016/j.devcel.2023.01.002 |
| Language: | English |
| Additional information: | © 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | ASOs, BBB, BNB, PNS, RNA-targeting therapeutics, Schwann cells, macrophages, pericytes, tactocytes, vasculature |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10164408 |
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