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ON is an early diagnostic sign in most <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> patients caused by damage to the optic nerve leading to visual dysfunction. Various features of both MS and ON can be studied following induction of experimental autoimmune encephalomyelitis (<jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content>), an animal model of <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>, in Lewis rats. Inflammation and cell death in the optic nerve, with subsequent damage to the retinal ganglion cells in the retina, are thought to correlate with visual dysfunction. Thus, characterizing the pathophysiological changes that lead to visual dysfunction in <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> animals may help develop novel targets for therapeutic intervention. We treated <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> animals with and without the calpain inhibitor calpeptin (<jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>). Our studies demonstrated that the Ca<jats:sup>2+<\/jats:sup>\u2010activated neutral protease calpain was upregulated in the optic nerve following induction of EAE at the onset of clinical signs (<jats:styled-content style=\"fixed-case\">OCS<\/jats:styled-content>) of the disease, and these changes were attenuated following treatment with <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>. These reductions correlated with decreases in inflammation (cytokines, <jats:styled-content style=\"fixed-case\">iNOS<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> COX<\/jats:styled-content>\u20102, and NF\u2010\u03baB), and microgliosis (i.e. activated microglia). We observed that calpain inhibition reduced astrogliosis (reactive astroglia) and expression of aquaporin 4 (<jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4). The balance of Th1\/Th2 cytokine production and also expression of the Th1\u2010related <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>5 and <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>3 chemokine receptors influence many pathological processes and play both causative and protective roles in neuron damage. Our data indicated that <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content> suppressed cytokine imbalances. Also, Bax:Bcl\u20102 ratio, production of tBid, <jats:styled-content style=\"fixed-case\">PARP<\/jats:styled-content>\u20101, expression and activities of calpain and caspases, and internucleosomal <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> fragmentation were attenuated after treatment with CP. Our results demonstrated that CP decreased demyelination [loss of myelin basic protein (<jats:styled-content style=\"fixed-case\">MBP<\/jats:styled-content>)] and axonal damage [increase in dephosphorylated neurofilament protein (de\u2010<jats:styled-content style=\"fixed-case\">NFP<\/jats:styled-content>)], and also promoted intracellular neuroprotective pathways in optic nerve in <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> rats. Thus, these data suggest that calpain is involved in inflammatory as well as in neurodegenerative aspects of the disease and may be a promising target for treating <jats:styled-content style=\"fixed-case\">ON<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/jnc.12064","type":"journal-article","created":{"date-parts":[[2012,10,25]],"date-time":"2012-10-25T12:31:41Z","timestamp":1351168301000},"page":"133-146","source":"Crossref","is-referenced-by-count":53,"title":["Calpain inhibitor attenuated optic nerve damage in acute optic neuritis in rats"],"prefix":"10.1111","volume":"124","author":[{"given":"Arabinda","family":"Das","sequence":"first","affiliation":[{"name":"Division of Neurology Department of Neurosciences Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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