Oligodendrocyte Lineage Cells in Chronic Demyelination of Multiple Sclerosis Optic Nerve

Abstract

Reports that chronically demyelinated multiple sclerosis brain and spinal cord lesions contained immature oligodendrocyte lineage cells have generated major interest aimed at the potential for promotion of endogenous repair. Despite the prominence of the optic nerve as a lesion site and its importance in clinical disease assessment, no detailed studies of multiple sclerosis-affected optic nerve exist. This study aims to provide insight into the cellular pathology of chronic demyelination in multiple sclerosis through direct morphological and immunohistochemical analysis of optic nerve in conjunction with observations from an experimental cat optic nerve model of successful remyelination. Myelin staining was followed by immunohistochemistry to differentially label neuroglia. Digitally immortalized sections were then analyzed to generate quantification data and antigenic phenotypes including maturational stages within the oligodendrocyte lineage. It was found that some chronically demyelinated multiple sclerosis optic nerve lesions contained oligodendroglial cells and that heterogeneity existed in the presence of myelin sheaths, oligodendrocyte maturational stages and extent of axonal investment. The findings advance our understanding of oligodendrocyte activity in chronically demyelinated human optic nerve and may have implications for studies aimed at enhancement of endogenous repair in multiple sclerosis.

Senolytic therapy alleviates Aβ-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer’s disease model

“…2). As damage to myelinating oligodendrocytes can be a stimulus for the recruitment of OPCs to lesion sites 14–16 , we examined the presence of myelin in Aβ plaques of APP/PS1 mouse brains using an anti-myelin basic protein (MBP) antibody. Whereas MBP immunoreactivity associated with presumptive axons was abundant in areas devoid of plaques, the Aβ plaques themselves exhibited little or no MBP immunoreactivity (see Supplementary Fig.…”

“…The third major type of glial cell is the oligodendrocytes, which arise from oligodendrocyte progenitor cells (OPCs). OPCs are a major population of cells in the brain, which are mobilized in response to neuronal injury and demyelination 13–16 . Despite their widespread presence throughout the brain, and their abilities to proliferate and move to and accumulate at sites of neuronal degeneration, the roles for OPCs in AD are unknown.…”

Evoked potentials as a biomarker of remyelination

“…Indeed, there have been very few neuropathological studies of the ONs in patients with MS (16,17). Thus, the interpretation of the myelin changes in the ON underpinning delayed latencies and decrease in amplitude of VEPs has largely relied on extrapolation from data on demyelination/remyelination of the spinal cord in animal models (2,18).…”

Optic Neuritis: A Model for the Immuno-pathogenesis of Central Nervous System Inflammatory Demyelinating Diseases

“…While reports on acute optic nerve lesions are scant, chronic ON lesions in humans have been examined in more detail. The pathology of established ON lesions greatly resembles chronic inactive MS plaques [24,25]. In a systematic study by Jennings and Carroll [25] eight optic nerves from four patients with MS were analyzed, encompassing 22 noncontiguous ON segments.…”

“…The pathology of established ON lesions greatly resembles chronic inactive MS plaques [24,25]. In a systematic study by Jennings and Carroll [25] eight optic nerves from four patients with MS were analyzed, encompassing 22 noncontiguous ON segments. Each lesion exhibited features of long-standing injury, with the defining characteristic being astrogliosis.…”