A Hypoxia-Inflammation Cycle and Multiple Sclerosis: Mechanisms and Therapeutic Implications.

Purpose of Review: Multiple sclerosis (MS) is a complex neurodegenerative disease characterized by inflammation, demyelination, and neurodegeneration. Significant hypoxia exists in brain of people with MS (pwMS), likely contributing to inflammatory, neurodegenerative, and vascular impairments. In this review, we explore the concept of a negative feedback loop between hypoxia and inflammation, discussing its potential role in disease progression based on evidence of hypoxia, and its implications for therapeutic targets. Recent Findings: In the experimental autoimmune encephalomyelitis (EAE) model, hypoxia has been detected in gray matter (GM) using histological stains, susceptibility MRI and implanted oxygen sensitive probes. In pwMS, hypoxia has been quantified using near-infrared spectroscopy (NIRS) to measure cortical tissue oxygen saturation (StO Summary: The hypoxia-inflammation cycle could exacerbate neuroinflammation and disease progression. We explore therapeutic approaches that target this cycle, providing information about potential treatments in MS. There are many therapeutic approaches that could block this cycle, including inhibiting hypoxia-inducible factor 1-α (HIF-1α), blocking cell adhesion or using vasodilators or oxygen, which could reduce either inflammation or hypoxia. This review highlights the potential significance of the hypoxia-inflammation pathway in MS and suggests strategies to break the cycle. Such treatments could improve quality of life or reduce rates of progression.