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Title: Structure, function and regulation of the blood nerve barrier
Author: Malong, Liza
ISNI:       0000 0004 8507 5449
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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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.
Supervisor: Lloyd, A. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available