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Open Access 01-12-2024 | Glioma | Research

Brain injury drives optic glioma formation through neuron-glia signaling

Authors: Jit Chatterjee, Joshua P. Koleske, Astoria Chao, Andrew D. Sauerbeck, Ji-Kang Chen, Xuanhe Qi, Megan Ouyang, Lucy G. Boggs, Rujuta Idate, Lara Isabel Marco Y Marquez, Terrence T. Kummer, David H. Gutmann

Published in: Acta Neuropathologica Communications | Issue 1/2024

Abstract

Tissue injury and tumorigenesis share many cellular and molecular features, including immune cell (T cells, monocytes) infiltration and inflammatory factor (cytokines, chemokines) elaboration. 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 Nf1-deficient preneoplastic progenitors. We further elucidate the underlying molecular and cellular mechanisms, whereby glutamate released from damaged neurons stimulates IL-1β release by oligodendrocytes to induce microglia expression of Ccl5, a growth factor critical for Nf1-OPG formation. Interruption of this cellular circuit using glutamate receptor, IL-1β or Ccl5 inhibitors abrogates injury-induced glioma progression, thus establishing a causative relationship between injury and tumorigenesis.

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Title: Brain injury drives optic glioma formation through neuron-glia signaling
Authors: Jit Chatterjee
Joshua P. Koleske
Astoria Chao
Andrew D. Sauerbeck
Ji-Kang Chen
Xuanhe Qi
Megan Ouyang
Lucy G. Boggs
Rujuta Idate
Lara Isabel Marco Y Marquez
Terrence T. Kummer
David H. Gutmann
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Glioma
Glioma
Glioma
Central Nervous System Trauma
Cytokines
Brain Tumor
Neurofibromatosis Type 1
Published in: Acta Neuropathologica Communications / Issue 1/2024
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-024-01735-w

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Springer Medicine

Brain injury drives optic glioma formation through neuron-glia signaling

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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