Glutamate-stressed cortical neurons induce leukemia inhibitory factor (LIF) gene expression in primary cortical astrocytes, by a mechanism dependent on astrocytic adenosine receptor activation. Supernatants of primary mouse cortical neurons (NS) collected 18 hours following treatment without (untr.) or with glutamate (glut.; 50 μM, for 1 hour) were applied (1:1 dilution by volume) to the primary cultured cortical astrocytes for 2 hours. Where indicated, astrocytes were pre-treated with caffeine (50 μM) or a cocktail of adenosine A2A and A2B receptor antagonists (A2A antagonist: ZM 241385, 250 nM; A2B antagonist: MRS 1754, 250 nM), for 30 minutes before incubation with neuronal supernatants and were analyzed for LIF mRNA expression (relative to GAPDH) using real-time PCR. Data are normalized to the control and presented as Mean ± SEM of three independent experiments. P < 0.05.