Immune contributions of the meninges and choroid plexus in animal models of central and peripheral nervous system neuropathy

The meninges have long been accepted as purely structural, protecting the central nervous system (CNS). Similarly, the choroid plexus (CP) was thought to only produce cerebrospinal fluid. Advances have dispelled these limited views, and the meninges and CP are now known as critical sites of immune activity, housing various immune cells, including B and T cells, monocytes/macrophages, and dendritic cells, and are increasingly implicated in neuroinflammation. The broad aim of this thesis is to characterise the immune profile of the meninges, CP, and secondary lymphoid tissue in animal models of CNS and peripheral neuropathy. New evidence in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, suggests inflammation of the meninges and CP changes are crucial for disease induction, warranting further investigation. Firstly, we demonstrated significant changes in the meninges and lymphoid tissue in EAE. Adoptive transfer of immunosuppressive activated regulatory T cells (Tregs) resulted in their migration to the pia and CP, and drainage from the CNS back into lymph nodes 2-4 days following delivery. Treg treatment at the peak of EAE showed mild changes in meningeal/lymphatic immunity. Secondly, to study meningeal involvement in peripheral neuropathy, where literature is severely lacking, we utilised an animal model of peripheral nerve injury, sciatic nerve chronic constriction injury (CCI), and 2 animal models of chemotherapy-induced peripheral neuropathy (CIPN). The immune profile of the meninges, CP, and lymphoid tissue was compared across male and female mice in acute stages of CCI and in a chronic model. We found the immune profile of the meninges, CP, and lymphoid tissue at acute stage of injury is different for males and females, is altered at 7 days and 21 days post-injury and appears to resolve by a chronic time point. In CIPN animal models, we demonstrated the immune profile of the meninges and CP is minimally affected, however, there were numerous significant changes in lymphoid organs. Together, results from this thesis provide comprehensive characterisation of immune cell profile in the meninges and CP in EAE and peripheral neuropathy models. Further research is warranted to ascertain precise mechanisms underlying their involvement.

Grantor dc:publisher

UNSW, Sydney

Year dc:date

2021

Author dc:creator

• Keating, Brooke

• Neuroinflammation
• Meninges
• Choroid plexus
• Neuropathy
• Neuroimmunology
• Animal models

Statement dc:rights

• open access
• CC BY-NC-ND 3.0
• free_to_read

Licence

• https://purl.org/coar/access_right/c_abf2
• https://creativecommons.org/licenses/by-nc-nd/3.0/au/

Language dc:language

EN

Identifier

https://doi.org/10.26190/unsworks/22718

OAI identifier oai:identifier

oai:unsworks.library.unsw.edu.au:1959.4/71102