A, Schematic of experimental design. B, C57BL/6J mice were cranially irradiated with 10 Gy of X-rays (3 mice per cohort). After 5 days, mice were treated with either vehicle or ABT-263 (50 mg/kg) daily for 25 days. Senescence was measured at 30 days post-IR by staining brain sections for SA-β-Gal activity. Representative Images of SA-β-Gal staining of the cortex of brains of cranially irradiated mice treated with vehicle or ABT-263 are shown. Scale bar=100 μm. C, Plot shows numbers of SA-β-Gal cells per 40X microscopic field in brains of vehicle or ABT-263 treated mice (n=3 for each cohort, P= 0.0072, error bars S.D). D, Representative Images of TUNEL staining of the cortex of brains of cranially irradiated mice treated with vehicle or ABT-263 are shown. Scale bar=100 μm. E, Plot shows number of TUNEL-positive cells per 40X microscopic field in brains of vehicle- or ABT-263-treated mice (n=3 for each cohort, P<0.0001, error bars S.D). F, C57BL/6J mice were mock irradiated or cranially irradiated with 10 Gy of X-rays (6 mice per cohort). After 5 days, mice were treated with either vehicle or ABT-263 (50 mg/kg) daily for 25 days. At 30 days post-IR, mice were intra-cranially implanted with 2,500 GL261 cells expressing firefly luciferase. Tumor growth was monitored by BLI imaging over a 30-day period. Plot represents average signal intensity (photons per second) for each cohort versus time post-injection. (P=0.0074, error bars S.E.M). Note marked delay in tumor growth (green line) in mouse brains pre-treated with ABT-263. G, Kaplan-Meier curves show survival of pre-irradiated mice, treated with vehicle or ABT-263, implanted with GL261 cells and then monitored over a 60-day period. (n=6 per cohort, P=0.0005). H, H&E-stained sections of GL261 tumors in pre-irradiated mouse brains treated with vehicle or ABT-263 prior to tumor cell implantation. Note: tumors in ABT-263-treated mice are highly necrotic with undefined borders. Scale bar =100 μM. I, Representative TUNEL images of GL261 tumors in vehicle or ABT-263 treated irradiated mouse brains. Scale bar=100 μm. J, Plot shows number of TUNEL-positive cells per 40X microscopic field in GL261 tumors in vehicle or ABT-263 treated mice (n=3 for each cohort, P=0.0184, error bars S.D).