Sevoflurane Exacerbates Cognitive Impairment Induced by A β 1-40 in Rats through Initiating Neurotoxicity, Neuroinflammation, and Neuronal Apoptosis in Rat Hippocampus.

Objective: This study was aimed at investigating whether sevoflurane inhalation induced cognitive impairment in rats with a possible mechanism involved in the event.

Methods: Thirty-two rats were randomly divided into four groups of normal saline (NS) + O2 , NS + sevoflurane (sevo), amyloid- β peptide (A β ) + O2 , and A β  + sevo. The rats in the four groups received bilateral intrahippocampus injections of NS or A β . The treated hippocampus was harvested after inhaling 30% O2 or 2.5% sevoflurane. Evaluation of cognitive function was performed by Morris water maze (MWZ) and an A β 1-42 level was determined by ELISA. Protein and mRNA expressions were executed by immunohistochemical (IHC) staining, Western blotting, and qRT-PCR.

Results: Compared with the NS-treated group, sevoflurane only caused cognitive impairment and increased the level of A β 1-42 of the brain in the A β -treated group. Sevoflurane inhalation but not O2 significantly increased glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule (IBA)1 expression in A β -treated hippocampus of rats. Expression levels for Bcl-xL, caspase-9, receptor for advanced glycation end products (RAGE) and brain-derived neurotrophic factor (BDNF) were significantly different in quantification of band intensity between the rats that inhaled O2 and sevoflurane in A β -treated groups (all P < 0.05). Interleukin- (IL-) 1 β , nuclear factor- κ B (NF- κ B), and inducible nitric oxide synthase (iNOS) mRNA expression increased after the rats inhaled sevoflurane in the A β -treated group (both P < 0.01). There were no significant differences in the change of GFAP, IBA1, Bcl-xL, caspase-9, RAGE, BDNF, IL-1 β , NF- κ B, and iNOS in the NS + O2 and NS + sevo group (all P > 0.05).

Conclusion: Sevoflurane exacerbates cognitive impairment induced by A β 1-40 in rats through initiating neurotoxicity, neuroinflammation, and neuronal apoptosis in rat hippocampus.