To investigate the effects of isoflurane and sevoflurane at the equivalent depth of subanesthesia on neuronal proliferation and phosphorylation of extraceullar signal-regulated kinase 1/2 (ERK1/2) protein in the hippocampi of neonatal rats.

Seventy-two neonatal rats at postnatal day 7 were involved in this study and they were assigned randomly into isoflurane group (Iso group), sevoflurane group (Sev group) and control group (Con group). The rats in I group, S group or C group were separately exposed to 0.75% isoflurane or 1.2% sevoflurane (equivalent to 0.3 MAC for neonatal rats) or air for 6 h. Some rats in each group were injected intraperitoneally BrdU 100 mg/kg immediately (D0) (n=6) or 3 days after exposure (D3) (n=6), and their brains were perfusion and embedded by paraffin 24 h after BrdU injection. BrdU positive expressions in the in dentate gyrus (DG) area of hippocampus were detected by IHC staining. Besides, the fresh hippocampi of some rats each group were dissected at the end of anesthesia, caspase-3 and phospho-ERK1/2, ERK1/2 proteins expression were detected by Western blot (n=6). The other rats in each group were used to measure changes of pH and blood glucose (n=6). One way ANOVA test was used for data analysis among groups.

BrdU-positive cells had no significant difference among group IsoD0((1332.43±192.70)/mm²), group SevD0((1207.33±139.50)/mm²), and group ConD0((1362.40±227.90)/mm²) at D0, while which had significantly decreased by 32.6% (P<0.05) in group IsoD3((604.56±65.77)/mm²) when compared with those in group ConD3((896.90±78.77)/mm²) at D3. There was no significant difference between groups of SevD3((808.73±41.27)/mm²) and ConD3. The expression of caspase-3 protein was increased by 195% (P<0.01) in Iso group while which only increased by 74% (P<0.05) in Sev group when compared with Con group. The expression of P44 and P42 of phospho-ERK1/2 protein in the hippocami decreased by 53% (P<0.01) and 47% (P<0.01)) seperately in Iso group when compared with Con group, while there were no significant differences between Sev group and Con group.

0.3 MAC isoflurane, not sevoflurane inhibits neuronal proliferation in DG of hippocampi in the neonatal rats. Inhibiting ERK1/2 phosphorylation may involve in the mechanisms of that isoflurane inhibits neuronal proliferation.

Isoflurane; Sevoflurane; Hippocampus; Neuronal proliferation