{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T18:06:48Z","timestamp":1789927608450,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,12,27]],"date-time":"2004-12-27T00:00:00Z","timestamp":1104105600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2005,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Children affected with the inherited tumor predisposition syndrome, neurofibromatosis 1 (NF1), are prone to the development of low\u2010grade astrocytic optic pathway tumors (optic pathway glioma [OPG]). Previously, we developed a model of NF1\u2010associated astrocytoma (<jats:italic>GFAPCre; Nf1<\/jats:italic><jats:sup><jats:italic>flox\/mut<\/jats:italic><\/jats:sup> mice) in which mice develop optic nerve and chiasm glioma. To define the molecular pathogenesis of OPG, we used this mouse model to study the natural history of OPG formation using immunohistological and radiographic approaches. We observed that whereas astrocyte hyperplasia is present in the optic nerves associated with gross optic nerve thickening at 3 weeks of age, overt neoplastic changes were not seen until 2 months of age. Astrocyte proliferation was maximal between 3 weeks and 2 months of age, suggesting that the most rapid period of growth occurs early. Mouse OPG tumors were detected by magnetic resonance imaging at 2 months of age and exhibited contrast enhancement, as seen in human OPG. In addition, the mouse OPG tumors exhibited expression of proteins associated with astroglial progenitors, including nestin and brain lipid binding protein. Last, we observed neovascularization and microglial cell infiltration by 3 weeks of age before overt neoplastic transformation, suggesting that these cellular changes participate in the early stages of tumor formation. Ann Neurol 2005;57:119\u2013127<\/jats:p>","DOI":"10.1002\/ana.20337","type":"journal-article","created":{"date-parts":[[2004,12,29]],"date-time":"2004-12-29T11:51:17Z","timestamp":1104321077000},"page":"119-127","source":"Crossref","is-referenced-by-count":63,"title":["Natural history of neurofibromatosis 1\u2013associated optic nerve glioma in mice"],"prefix":"10.1002","volume":"57","author":[{"given":"M. Livia","family":"Bajenaru","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel R.","family":"Garbow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie","family":"Perry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Rosario","family":"Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Gutmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,12,27]]},"reference":[{"key":"e_1_2_6_2_2","volume-title":"Neurofibromatosis: phenotype, natural history, and pathogenesis","author":"Friedman JM","year":"1999"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(95)70159-1"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410410204"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(94)70122-9"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20211"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2003.06.008"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/61.3.215"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.53.12.793"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1966.00470110011002"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19930801)72:3<856::AID-CNCR2820720335>3.0.CO;2-K"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1080\/02688690310001601216"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-8994(02)00628-8"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11119"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.74.877.740024"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004310000531"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg016"},{"key":"e_1_2_6_18_2","article-title":"Late\u2010onset optic pathway tumors in children with neurofibromatosis 1 (NF1)","author":"Listernick R","journal-title":"Neurology"},{"key":"e_1_2_6_19_2","first-page":"8573","article-title":"Optic nerve glioma in mice requires astrocyte Nf1 gene inactivation and Nf1 brain heterozygosity","volume":"63","author":"Bajenaru ML","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004010051161"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.9.1019"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.862101"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910360612"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201740"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00686074"},{"key":"e_1_2_6_26_2","first-page":"2521","article-title":"Immunohistochemical properties of human optic nerve glioma. 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