Inhibition of the ERK1/2 pathway blocks BDNF-mediated neuroprotection against neonatal H-I. P7 rats were treated with VEH:VEH, VEH:BDNF, orU0126:BDNF before the carotid ligation and exposure to hypoxia for 2.5 hr. One week later, animals were killed, and brain sections were stained with cresyl violet. A, Examples of the degree of injury of representative animals from each treatment group are shown. Note the marked unilateral hemispheric tissue loss in the cortex and hippocampus in VEH:VEH andU0126:BDNF animals, whereas there is little to no tissue loss in the VEH:BDNF animal. B,BDNF-mediated neuroprotection was significantly inhibited by U0126. Regional area loss from the striatum, hippocampus, and cortex of each group was assessed as described in Materials and Methods. Data represent the mean ± SEM; *p < 0.05 comparing VEH:BDNF with either theVEH:VEH or the U0126:BDNF group. Data were analyzed by ANOVA and Dunn's multiple comparison method.