title: Isoflurane induces learning impairment that is mediated by interleukin 1β in rodents.
abstract: Postoperative cognitive decline is a clinical syndrome. Volatile anesthetics are commonly used during surgery. It is conceivable that volatile anesthetics may contribute to postoperative cognitive decline. Isoflurane can impair cognitive functions of animals under certain conditions. However, the mechanisms for this impairment are not clear. Here, male 18-month old Fisher 344 rats or 10-week old mice were exposed to 1.2 or 1.4% isoflurane for 2 h. Our studies showed that isoflurane impaired the cognitive functions of the rats in Barnes maze. Isoflurane-exposed rats had reduced freezing behavior during the training sessions in the fear conditioning test. This isoflurane effect was attenuated by lidocaine, a local anesthetic with anti-inflammatory property. Rats that had training sessions and were exposed to isoflurane 30 min later had freezing behavior similar to that of control animals. Isoflurane increased the expression of interleukin 1β (IL-1β), interleukin-6 and activated caspase 3 in the hippocampus of the 18-month old rats. IL-1β positive staining was co-localized with that of NeuN, a neuronal marker. The increase of IL-1β and activated caspase 3 but not interleukin-6 was attenuated by lidocaine. Isoflurane also impaired the cognitive functions of 10-week old C57BL/6J mice and increased IL-1β in their hippocampi. However, isoflurane did not affect the cognitive functions of IL-1β deficient mice. Our results suggest that isoflurane impairs the learning but may not affect the recall of the aged rats. IL-1β may play an important role in this isoflurane effect.
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Cao
authors.forename: Liaoliao
authors.initials: L
authors.lastname: Li
authors.forename: Daowei
authors.initials: D
authors.lastname: Lin
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D019570:Inhalation Exposure; D053583:Interleukin-1beta / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology*; D007859:Learning Disabilities / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D018782:Maze Learning; D011939:Mental Recall / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D016708:Synaptophysin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D039481:CD11b Antigen; D053583:Interleukin-1beta; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C546339:Rbfox3 protein, rat; D016708:Synaptophysin; D014409:Tumor Necrosis Factor-alpha; C053386:drebrins; D007530:Isoflurane; D053148:Caspase 3