Bax^−/− oligodendrocytes are resistant to excitotoxic insults. A, Oligodendrocyte cultures were obtained from optic nerves of 12-d-old Bax^+/+, Bax^+/−, or Bax^−/− mice and used for toxicity assays after 1 d in vitro. Activation of AMPA receptors with 10 μm AMPA plus 100 μm cyclothiazide for 15 min caused oligodendroglial excitotoxicity in wild-type and Bax^+/− cells, while Bax^−/− oligodendrocytes were totally resistant to this insult. In addition, maximal activation of high- or low-affinity kainate (KA) receptors by 3 μm or 3 mm kainate plus GYKI53655 caused cell death, which was significantly diminished in oligodendrocytes obtained from Bax^+/− or Bax-null mice. *p < 0.05, **p < 0.01, ***p < 0.001, compared with Bax^+/+ oligodendrocytes. B, Microphotographs representing AMPA toxicity in oligodendrocytes derived from wild-type or Bax^−/− mice. Cells were treated as indicated above and stained with calcein-AM (green, living cells) and propidium iodide (red, dead cells) to quantify the effect of agonists. C, Caspase-9 and caspase-3 activation in Bax^+/+ and Bax^−/− oligodendrocytes after exposure to AMPA or kainate. Activation of AMPA and kainate receptors caused activation of caspase-9 and caspase-3 in wild-type oligodendrocytes but not in Bax^−/− oligodendrocytes, as determined by immunocytochemistry with antibodies to cleaved caspase-9 or caspase-3, respectively. *p < 0.05, **p < 0.01, ***p < 0.001, compared with Bax^+/+ oligodendrocytes.