Reactive microglia in dysmyelination and demyelination

The relationship between microglial activation and dysmyelination/demyelina tion was analyzed in a long-lived myelin mutant, the Long Evans shaker (les ) rat, which exhibits early dysmyelination and a later loss of abnormal mye lin sheaths. A microglial reaction characterized by progressive morphologic al transformation and increasing cell density was localized exclusively to white matter during postnatal 2-4 weeks, suggesting a microglial response t o dysmyelination and oligodendroglial pathology. A further microglial react ion as marked by microglial expression of MHC II and a concomitant expressi on in the brain and spinal cord of mRNA for interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide syntha se (iNOS) began around 4 weeks when the remaining myelin was lost. Ultrastr ucturally, activated microglia ingested numerous myelin figures, suggestive of active phagocytosis. Thus, this study indicates that microglial reactio n is graded in chronic neurological disorders and suggests that MHC II expr ession marks a functional change of activated microglia. GLIA 34:101-109, 2 001. (C) 2001 Wiley-Liss, Inc.