Oligodendrocytes and the early multiple sclerosis lesion

Area of Science:

• Neuropathology
• Immunopathology
• Neuroimmunology

Background:

• Oligodendrocyte loss timing and nature in multiple sclerosis (MS) lack consensus.
• Acute oligodendrocyte loss in new MS lesions involves specific immunopathological changes.
• MS and neuromyelitis optica (NMO) share pathological similarities, including demyelination secondary to oligodendrocyte apoptosis.

Purpose of the Study:

• To describe the immunopathology of acute oligodendrocyte loss in new MS lesions.
• To investigate the cellular and molecular changes associated with oligodendrocyte injury in MS.
• To explore the potential autoimmune basis of MS by comparing it to NMO.

Main Methods:

• Review of 23 severe early MS cases from 300 autopsies.
• Histopathological analysis of new MS lesions.
• Immunohistochemical staining for caspase 3, immunoglobulin (IgG), and complement.

Main Results:

• Oligodendrocytes in prephagocytic lesions show apoptosis (caspase 3 positive), phagocytosis, swelling, abnormal nuclei, complement deposition, and lysis.
• Associated findings include IgG(+) microglia, early macrophages, inflammatory demyelination, open blood-brain barrier, and rare CD8 T cells.
• Myelin contacted by macrophages is complement-reactive but not IgG-reactive, suggesting scavenging of nonvital myelin.

Conclusions:

• Oligodendrocyte injury in MS lesions is nonspecific, with apoptosis being a key feature.
• The pathological resemblance to NMO suggests MS might be an autoimmune disease.
• Oligodendrocyte apoptosis in MS could be triggered by injury to other glial or mesenchymal components.