Brain injury drives optic glioma formation through neuron-glia signaling.
Jit ChatterjeeJoshua P KoleskeAstoria ChaoAndrew D SauerbeckJi-Kang ChenXuanhe QiMegan OuyangLucy G BoggsRujuta IdateLara Isabel Marco Y MarquezTerrence T KummerDavid H GutmannPublished in: Acta neuropathologica communications (2024)
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.
Keyphrases
- brain injury
- optic nerve
- subarachnoid hemorrhage
- growth factor
- signaling pathway
- traumatic brain injury
- optical coherence tomography
- oxidative stress
- lps induced
- cerebral ischemia
- pi k akt
- poor prognosis
- nuclear factor
- liver injury
- stem cells
- drug induced
- spinal cord
- squamous cell carcinoma
- case report
- dendritic cells
- binding protein
- adipose tissue
- metabolic syndrome
- cell proliferation
- high glucose
- stress induced
- spinal cord injury