Project R-13614

High salt diet causes blood-brain barrier disturbances in multiple sclerosis: involvement of the renin-angiotensin-aldosterone system. (Research)

Multiple sclerosis (MS) is a chronic neuro-inflammatory disorder that is characterized by immune cells infiltrating the brain and spinal cord, thereby causing demyelination and neurodegeneration. In healthy conditions, the blood brain barrier (BBB) prevents this from happening, while in patients with MS, the BBB is functionally and structurally impaired. Recent studies have indicated that a high salt diet impacts the pathogenesis of MS, by influencing the immune compartment. In addition, the renin-angiotensin-aldosterone system (RAAS) is implicated in salt retention and regulation of blood pressure. Interestingly, RAAS inhibition improves MS-like disease in mice, and components of the RAAS are found in cells that regulate BBB function. Therefore, we hypothesize that high salt diet, directly or through dysregulation of RAAS homeostasis in the neurovascular unit (NVU), leads to enhanced BBB disruption and exacerbation of neuro-inflammatory processes in MS. In this project, a combination of human in vitro and ex vivo studies is employed to understand the interplay between RAAS homeostasis in the NVU, high salt diet, and neuro-inflammatory pathways in MS. Obtained results will generate novel, highly informative knowledge on dietary influences on disease, in particular MS.

01 January 2023 - 31 December 2025