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Their common pathobiology raises the intriguing possibility that brain injury could create a tissue microenvironment permissive for tumor formation. Leveraging several murine models of the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome and two experimental methods of brain injury, we demonstrate that both optic nerve crush and diffuse traumatic brain injury induce optic glioma (OPG) formation in mice harboring <jats:italic>Nf1<\/jats:italic>-deficient preneoplastic progenitors. We further elucidate the underlying molecular and cellular mechanisms, whereby glutamate released from damaged neurons stimulates IL-1\u03b2 release by oligodendrocytes to induce microglia expression of Ccl5, a growth factor critical for <jats:italic>Nf1<\/jats:italic>-OPG formation. Interruption of this cellular circuit using glutamate receptor, IL-1\u03b2 or Ccl5 inhibitors abrogates injury-induced glioma progression, thus establishing a causative relationship between injury and tumorigenesis.<\/jats:p>","DOI":"10.1186\/s40478-024-01735-w","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T16:02:42Z","timestamp":1706889762000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Brain injury drives optic glioma formation through neuron-glia signaling"],"prefix":"10.1186","volume":"12","author":[{"given":"Jit","family":"Chatterjee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua P.","family":"Koleske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astoria","family":"Chao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Sauerbeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Kang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanhe","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy G.","family":"Boggs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rujuta","family":"Idate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara Isabel","family":"Marco Y Marquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terrence T.","family":"Kummer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3127-5045","authenticated-orcid":false,"given":"David H.","family":"Gutmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,2]]},"reference":[{"key":"1735_CR1","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1186\/s13104-017-2459-2","volume":"10","author":"V Albert","year":"2017","unstructured":"Albert V, Subramanian A, Agrawal D, Bhoi SK, Pallavi P, Mukhopadhayay AK (2017) RANTES levels in peripheral blood, CSF and contused brain tissue as a marker for outcome in traumatic brain injury (TBI) patients. 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