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Until recently, <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content> was considered an acute aggressive variant of multiple sclerosis (<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>), despite the fact that early studies postulated that <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> may be two distinct diseases with a common clinical picture. With the discovery of a highly specific serum autoantibody (<jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IgG<\/jats:styled-content>), Lennon and colleagues provided the first unequivocal evidence distinguishing <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content> from <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> and other central nervous system (<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>) inflammatory demyelinating disorders. The target antigen of <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IgG<\/jats:styled-content> was confirmed to be aquaporin\u20104 (<jats:styled-content style=\"fixed-case\">AQP4<\/jats:styled-content>), the most abundant water channel protein in the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>, mainly expressed on astrocytic foot processes at the blood\u2013brain barrier, subpial and subependymal regions. Pathological studies demonstrated that astrocytes were selectively targeted in <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content> as evidenced by the extensive loss of immunoreactivities for the astrocytic proteins, <jats:styled-content style=\"fixed-case\">AQP4<\/jats:styled-content> and glial fibrillary acidic protein (<jats:styled-content style=\"fixed-case\">GFAP<\/jats:styled-content>), as well as perivascular deposition of immunoglobulins and activation of complement even within lesions with a relative preservation of myelin. In support of these pathological findings, <jats:styled-content style=\"fixed-case\">GFAP<\/jats:styled-content> levels in the cerebrospinal fluid (<jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>) during acute <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content> exacerbations were found to be remarkably elevated in contrast to <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> where <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">GFAP<\/jats:styled-content> levels did not substantially differ from controls. Additionally, recent experimental studies showed that <jats:styled-content style=\"fixed-case\">AQP4<\/jats:styled-content> antibody is pathogenic, resulting in selective astrocyte destruction and dysfunction <jats:styled-content style=\"fixed-case\"><jats:italic>in vitro<\/jats:italic><\/jats:styled-content>, <jats:styled-content style=\"fixed-case\"><jats:italic>ex vivo<\/jats:italic><\/jats:styled-content> and <jats:styled-content style=\"fixed-case\"><jats:italic>in vivo<\/jats:italic><\/jats:styled-content>. These findings strongly suggest that <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content> is an autoimmune astrocytopathy where damage to astrocytes exceeds both myelin and neuronal damage. This chapter will review recent neuropathological studies that have provided novel insights into the pathogenic mechanisms, cellular targets, as well as the spectrum of tissue damage in <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/bpa.12099","type":"journal-article","created":{"date-parts":[[2013,12,18]],"date-time":"2013-12-18T07:06:01Z","timestamp":1387350361000},"page":"83-97","source":"Crossref","is-referenced-by-count":391,"title":["The Pathology of an Autoimmune Astrocytopathy: Lessons Learned from Neuromyelitis Optica"],"prefix":"10.1111","volume":"24","author":[{"given":"Claudia F.","family":"Lucchinetti","sequence":"first","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan F. 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