Axonal dystrophy as a consequence of long-term demyelination.
Central nervous system lesions in guinea pigs sensitized for chronic relapsing experimental allergic encephalomyelitis for between 18 and 36 months have been found to possess a small but probably significant degree of axonal involvement. Axonal identity was established by light and electron microscopy and immunocytochemistry. The axonal changes were restricted to white matter and consisted of massive (up to 95 microns) scattered axonal spheroids which displayed lateral branches and vacuoles; small groups of spheroids filled with a wide assortment of axoplasmic organelles; and deeper, more extensive collections of affected demyelinated axons and spheroids which frequently displayed abortive axonal regeneration into the Virchow-Robin space. Although accumulations of most axoplasmic organelles occurred in the spheroids and reactive axons, microtubules were relatively rare. These formations were never seen in adjacent unaffected white matter and spinal cord tissue from normal aged animals contained only the occasional spheroid. It is hypothesized that the disease process in experimental allergic encephalomyelitis may be more dynamic than previously described and that prolonged interruption in normal axon-glial relationships in chronically demyelinated (sometimes remyelinated) gliotic lesions might lead to a block in axoplasmic transport and a disruption of the axonal cytoskeleton. Although most affected axons appeared intact, some of the spheroids probably represented proximal stumps from which sprouting occurred, leading to neuroma-like formations. The implications of the findings are discussed in reference to long-term demyelination and multiple sclerosis where almost identical profiles have been documented.
Raine
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CS
Department of Pathology, Rose F. Kennedy Center for Research in Mental Retardation and Human Development, Albert Einstein College of Medicine, Bronx, New York.
Cross
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AH
D000818:Animals; D001369:Axons / Q000473:pathology* / Q000648:ultrastructure; D002490:Central Nervous System / Q000473:pathology* / Q000648:ultrastructure; D003711:Demyelinating Diseases / Q000473:pathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology; D005260:Female; D006168:Guinea Pigs; D008297:Male; D008854:Microscopy, Electron; D009103:Multiple Sclerosis / Q000473:pathology; D009186:Myelin Sheath / Q000503:physiopathology*