Glutamate-elicited OL death does not involve apoptotic signaling mechanisms. OLs were treated with glutamate alone and in the presence of 1 mM cystine (A) or 30 μM ZVAD-fmk (B) for 24 h and cell survival was determined. Data are mean ± SE, *P < 0.05, n = 9. C: OLs were treated with glutamate with/without 30 μM Z-VAD-fmk for 24 h and caspase 3/7 activity was measured. Data are mean ± SE, n = 6. D: Cells were exposed to 1 mM glutamate in the presence of the necroptosis inhibitors, necrostatin-1 (Nec-1) and necrostatin-1s (Nec-1s), GSK-872, a RIP3 kinase inhibitor, and an IDO inhibitor. Cell survival was determined 24 h later. Data are mean ± SE, *P < 0.05, n = 9.