Fig. 6

Increased a glutamate (ELISA) and b Il-1β mRNA (qPCR) expression in the optic nerves of Nf1^flox/flox; hGFAP-Cre mice at 3 months of age following optic nerve crush at 6 weeks of age (ON-CR). c Memantine hydrochloride treatment (20 mg/kg) of Nf1^flox/flox; hGFAP-Cre mice for two weeks immediately after ON-CR at 6 weeks of age reduces d optic nerve proliferation (%Ki67⁺ cells; n = 5) when analysed at 12 weeks of age. Memantine treatment decreases e Il-1β and f Ccl5 mRNA expression (qPCR; n = 3). g Mechanistic model comparing the cellular and molecular events that induce gliomagenesis following injury (left side) and during spontaneous tumor formation (right side). (LEFT) ON-CR induces retinal ganglion cell glutamate release, which stimulates oligodendrocytes to release IL-1β, resulting in NFκB-dependent TAM Ccl5 expression and culminating in Nf1-OPG formation and growth. (RIGHT) T cells are induced to express Ccl4, which stimulates TAM production of Ccl5 and Nf1-OPG formation and growth. Data are presented as the means ± SEM. Scale bars: d 50 µm. Two-tailed Student’s t test