In multiple sclerosis (MS), immune cells breach the blood-brain barrier (BBB) and attack the central nervous system (CNS), causing significant neuroinflammation and demyelination. People with MS also experience neurovascular pathology, including BBB leakage, reduced blood flow and neurovascular uncoupling. In the CNS, these vascular functions are maintained by a multicellular structure known as the neurovascular unit, comprised primarily of endothelial cells, pericytes and astrocytes. The impact of inflammatory demyelination on cells within the neurovascular unit remains poorly understood.

To investigate the impact of MS-like pathology on the neurovascular unit, we utilised the cuprizone-autoimmune encephalomyelitis (CAE) model of inflammatory demyelination. CAE was induced by feeding mice 0.2% (w/w) cuprizone in powdered chow for two weeks to biochemically alter myelin, followed by stimulation of the peripheral immune system with complete Freund’s adjuvant and pertussis toxin. After 21 days, immunohistochemistry confirmed peripheral immune cell (T cell) infiltration, oligodendrocyte loss, and demyelination in the brains of CAE mice. Immunohistochemistry also revealed the disruption of neurovascular cells following CAE. There was a reduction in AQP4⁺ astrocytic endfeet coverage of the endothelium. Furthermore, CD13⁺ pericyte soma density was significantly decreased, despite an increase in pericyte coverage of blood vessels. CD31⁺ vessel morphology was also impacted, with vessels exhibiting reduced density, length and width, suggesting significant endothelial cell changes following CAE induction. These findings suggest immune-mediated demyelination in the brain significantly disrupts the cellular integrity of the neurovascular unit. Protecting cells of the neurovascular unit may be an attractive therapeutic approach to maintain vascular integrity in MS.