Prolonged exposure to volatile anesthetics causes neurodegeneration in developing animal brains. However, their underlying mechanisms of action remain unclear. The current study investigated the expression of proteins associated with the mitogen‑activated protein kinases (MAPK) and protein kinase B (Akt)/glycogen synthase kinase‑3β (GSK‑3β)/collapsin response mediator protein 2 (CRMP‑2) signaling pathways in the cortices of neonatal mice following exposure to sevoflurane. Seven‑day‑old (P7) neonatal C57BL/6 mice were randomly divided into 2 groups and either exposed to 2.6% sevoflurane or air for 6 h. Terminal deoxyribonucleotide transferase mediated dUTP nick end labeling (TUNEL) staining, as well as the expression of activated caspase‑3 and α‑fodrin, was used to detect neuronal apoptosis in the cortices of mice. MAPK signaling pathways were investigated by detecting the expression of phosphorylated (p‑) extracellular signal‑regulated kinase 1/2 (ERK1/2), p‑cyclic adenosine monophosphate response element‑binding protein (CREB), p‑p38, p‑nuclear factor (NF‑κB) and p‑c‑Jun N‑terminal kinase (p‑JNK). Akt/GSK‑3β/CRMP‑2 signaling pathways were assessed by detecting the expression of p‑Akt, p‑GSK‑3β and p‑CRMP‑2 in the cortices of P7 mice 2 h following exposure to sevoflurane. The results demonstrated that sevoflurane significantly increased the apoptosis of cells in the retrosplenial cortex (RS), frontal cortex (FC) and parietal association cortex (PtA), increased the expression of cleaved caspase‑3 expression and promoted the formation of 145 kDa and 120 kDa fragments from α‑fodrin. Sevoflurane inhibited the phosphorylation of ERK1/2 and CREB, stimulated the phosphorylation of p38 and NF‑κB, but did not significantly affect the phosphorylation of JNK. Furthermore, sevoflurane inhibited the phosphorylation of Akt, decreased the phosphorylation of GSK‑3β at ser9 and increased the phosphorylation of CRMP2 at Thr514. These results suggest that multiple signaling pathways, including ERK1/2, P38 and Akt/GSK‑3β/CRMP‑2 may be involved in sevoflurane‑induced neuroapoptosis in the developing brain.

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