Fig. 2: OL injury in Multiple Sclerosis.

a Oligodendrocytes in healthy conditions rely on nutrients (e.g., glucose), lipids (e.g., cholesterol, fatty acids), and growth factors to support their survival and myelination. b Acute-lethal injury is observed in acute MS lesions driven by cytotoxic T and NK cells (contact dependent), reactive astrocytes, microglia and increased fibrinogen. c Sub-lethal injury to oligodendrocytes in active MS lesions involves process retraction with retention of cell bodies, which can be reversed by returning them to optimal conditions. Important contributors to sub-lethal injury include metabolic stress, glutamate, and inflammatory mediators. Susceptibility to such injury may be influenced by age, and oligodendrocyte subpopulations may be specifically vulnerable. d Combination of insults and age can convert sublethal responses to progressive loss. Ongoing loss of oligodendrocytes is regulated via cell death mechanisms during disease progression, changes to the extracellular milieu such as modifications to the extracellular matrix (ECM) and presence of cytotoxic long chain fatty acids. Created using BioRender.com.