Induction of oligodendrocyte proliferation and remyelination after chronic demyelination: relevance to multiple sclerosis

• Published in: Laboratory investigation Vol. 59; no. 4; pp. 467 - 476
• Main Authors: RAINE, C. S, MOORE, G. R. W, HINTZEN, R, TRAUGOTT, U
• Format: Journal Article
• Language: English
• Published: New York, NY Nature Publishing 01.10.1988
• Subjects: Animals; Autoimmune Diseases - pathology; Autoimmune Diseases - physiopathology; Autoimmune Diseases - therapy; Biological and medical sciences; Chronic Disease; Encephalomyelitis, Autoimmune, Experimental - pathology; Encephalomyelitis, Autoimmune, Experimental - physiopathology; Encephalomyelitis, Autoimmune, Experimental - therapy; Female; Galactosylceramides - therapeutic use; Guinea Pigs; Immunohistochemistry; Male; Medical sciences; Multiple Sclerosis - pathology; Multiple Sclerosis - physiopathology; Multiple Sclerosis - therapy; Myelin Basic Protein - therapeutic use; Myelin Sheath - pathology; Myelin Sheath - physiology; Myelin Sheath - ultrastructure; Nervous system involvement in other diseases. Miscellaneous; Neuroglia - physiology; Neurology; Oligodendroglia - pathology; Oligodendroglia - physiology; Oligodendroglia - ultrastructure; Optic Nerve - pathology; Optic Nerve - physiopathology; Optic Nerve - ultrastructure; Recurrence; Spinal Cord - pathology; Spinal Cord - physiopathology; Immunohistochemistry; Spinal cord; Multiple sclerosis; Nervous system diseases; Optic nerve; Encephalomyelitis; Myelin; Exploration; Autoimmune disease; Inflammatory disease; Pathology; Regeneration; Chronic; Experimental disease; Oligodendrocyte; Demyelination; Animal; Morphometry
• ISSN: 0023-6837; 1530-0307

Optic nerve and spinal cord tissue from untreated guinea pigs with chronic relapsing experimental autoimmune encephalomyelitis, guinea pigs with experimental autoimmune encephalomyelitis in which the disease was treated with injections of myelin basic protein (MBP) combined with galactocerebroside (GC), and normal guinea pigs, has been studied morphologically, immunocytochemically and morphometrically. MBP/GC treatment induced widespread proliferation of oligodendrocytes and extensive central nervous system (CNS) remyelination in tissue from both sites. Whereas some oligodendrocytes within lesions from treated animals appeared to be derived from surviving cells which underwent mitosis, the frequent occurrence of nests of oligodendrocytes at the periphery of nerve fiber fascicles in optic nerve among perivascular astrocytic elements, raises the possibility that remyelinating oligodendrocytes might possess progenitors located in these regions. Observations from multiple sclerosis lesions showed that oligodendrocyte proliferation and CNS remyelination occur in human subcortical white matter, but to a lesser degree than that seen in the CNS of MBP/GC/treated guinea pigs. Immunocytochemical examination of CNS tissue from experimental autoimmune encephalomyelitis animals confirmed the morphologic identification of oligodendroglia. Preliminary morphometric analysis confirmed the impression of an increase in oligodendroglial cells in MBP/GC-treated animals. This increase was somewhat obscured statistically by a concomitant rise in the number of fibrous astrocytes. In view of the ability of oligodendrocytes to proliferate and produce new myelin in multiple sclerosis, the possibility is raised that an experimental immunologic approach similar to that employed here might have a beneficial effect in the human disease.