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We hypothesized that transient immunosuppression after initiation of MS\u2010like autoimmune mechanisms would disassociate development of MS\u2010like myelinated axon pathology from development of CNS inflammation in a rat model of autoimmune optic neuritis (AON). A rat model of myelin oligodendrocyte glycoprotein peptide\u2010induced AON was transiently treated (on days 3\u20137 after antigen exposure) with 5\u2010(4\u2010phenylbutoxy)psoralen (PAP\u20101), an immunomodulatory drug previously shown specifically to suppress proliferation of effector memory T\u2010cells and immunoglobulin class\u2010switched B\u2010cells. Thirteen days after antigen exposure, optic nerves were harvested for quantitative assessment of 12 MS\u2010associated pathologies using microfluorimetry. With one exception, the immunoreactivities (\u2010ir) for eight markers of MS\u2010like neuroinflammation and immune infiltration were significantly reduced (<jats:italic>P<\/jats:italic>&lt; 0.05) by transient PAP\u20101 treatment, often to levels significantly below those detected in normal control rat optic nerves. With one exception, four immunoreactive markers of MS\u2010like myelinated axon pathology were detected at levels indicating increased axon\/myelin pathology compared with vehicle\u2010treated rats with AON (<jats:italic>P<\/jats:italic>&lt; 0.05). These data suggest the conclusion that early causative mechanisms in CNS autoimmunity initiate signaling mechanisms that diverge into two separate pathways, one that is strongly associated with inflammatory responses and one that is associated predominantly with disturbed axon\u2010myelin interactions and impaired fast axonal transport. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.21645","type":"journal-article","created":{"date-parts":[[2008,3,11]],"date-time":"2008-03-11T20:56:26Z","timestamp":1205268986000},"page":"2111-2124","source":"Crossref","is-referenced-by-count":3,"title":["Transient 5\u2010(4\u2010phenylbutoxy)psoralen (PAP\u20101) treatment dissociates developing pathologies in autoimmune optic neuritis into two distinct pathology profiles"],"prefix":"10.1002","volume":"86","author":[{"given":"Martha 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