Malong, Liza;
(2019)
Structure, function and regulation of the blood nerve barrier.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The specialised blood barriers of the nervous system are important for protecting the neural environment but can hinder therapeutic accessibility. Studies in the central nervous system (CNS) have shown the importance of the cellular components of the neuro-vascular unit for blood brain barrier (BBB) function. Whilst the endothelial cells (ECs) confer barrier function with specialised tight junctions and low levels of transcytosis, pericytes and astrocytes provide complete coverage of the endothelial cells and both deliver essential signals for the development and maintenance of the BBB. In contrast, the blood nerve barrier (BNB) of the peripheral nervous system (PNS) remains poorly defined. In this thesis, we define the cells that constitute the BNB of the PNS and find that the vascular unit of peripheral nerve has a distinct cellular composition to the vascular unit of the brain with only partial coverage of the endothelial cells. We show that the BNB, while less tight than the BBB, is maintained by low levels of transcytosis and the tight junctions of the ECs. Importantly, we found that while ECs of the PNS have higher transcytosis levels than those of the CNS, the barrier is reinforced by resident macrophages that specifically engulf leaked material. This identifies a distinct role for macrophages as an important component of the BNB acting to protect the PNS environment with implications for improving therapeutic delivery to this protected tissue. Using an inducible mouse model in which Schwann cells can trigger the opening of the BNB, we show that opening the barrier is associated with increased transcytosis and that the transcription factor c-jun plays a key role in this process. Together, the results presented in this thesis provide new insights into the structure, function and regulation of the BNB with important implications for our understanding of PNS biology in health and following injury.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Structure, function and regulation of the blood nerve barrier |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices 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.ucl.ac.uk/id/eprint/10082817 |
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