Brain-derived neurotrophic factor (BDNF) and dexmedetomidine protective effects in glutamate agonist-induced in vivo and in vitro models. (A) Picture showing the excitotoxic ibotenate-induced lesions. Ibotenate (10 μg in 2μl) was injected intracerebrally to 5-day-old mouse pups. The pups were sacrificed on postnatal day 10 and their brains were embedded in paraffin before sectioning. (B) Effect of BDNF in excitotoxic challenge to mouse pups with ibotenate-induced lesions. **P < 0.01 versus phosphate-buffered saline (PBS). (C) Effect of increasing concentrations of BDNF (PBS, 0.3, 1, and 10 μm) in excitotoxic challenge (ibotenate 300 μm) to primary cortical isolated neuronal cultures on day in vitro (DIV) 12 with ibotenate-induced toxicity. *P < 0.05 and ***P < 0.001 versus PBS by ANOVA with post hoc analysis. (D) Effect of intraperitoneal injection of dexmedetomidine (DEX, 3 μg/kg) 1 h before excitotoxic challenge to pups mice with ibotenate-induced lesions. **P < 0.01 versus PBS. (E–F) Effect of increasing concentrations of dexmedetomidine (none, 0.3, 1, and 10 μm) in excitotoxic challenge (ibotenate 300 μm) to primary cortical isolated neuronal cultures at DIV 12 (E) and at DIV 7 (F) with ibotenate-induced cell death. *P < 0.05, **P < 0.01 versus PBS by ANOVA with post hoc analysis. (G) Effect of increasing concentrations of fetal calf serum (PBS, 0.4% and 4%) on dexmedetomidine’s neuroprotective effect in excitotoxic challenge (ibotenate 300 μm). *P < 0.05, **P < 0.01 versus PBS. (H) Effect of yohimbine (10 μm) in dexmedetomidine’s protective effect in excitotoxic challenge (ibotenate 300 μm). **P < 0.01 versus PBS, ## P < 0.01 versus DEX 1 μm by ANOVA with post hoc analysis. The bars represent the mean length of the lesion along the sagittal fronto-occipital axis ± SD for in vivo experiments, and the cell viability ratio ± SD, corresponding to the percent of the controls (ibotenate 300 μm defined as 100% of cell viability) for in vitro experiments. FCS = fetal calf serum; YO = yohimbine.