title: Isoflurane induces hippocampal cell injury and cognitive impairments in adult rats.
abstract: Post-operative cognitive dysfunction (POCD) is a clinical phenomenon characterized with cognitive decline in patients after anesthesia and surgery. It has been shown that interleukin-1β (IL-1β) contributes to the cognitive impairment of mice after surgery and isoflurane anesthesia. This study is designed to determine whether isoflurane alone increases inflammatory cytokines and causes cell injury and cognitive impairment. Four-month-old male Fisher 344 rats were exposed to or were not exposed to 1.2% isoflurane for 2 h. Two weeks later, rats were subjected to Barnes maze and fear conditioning tests. Although animals exposed to or non-exposed to isoflurane developed spatial learning, animals exposed to isoflurane had significant impairments in long-term spatial memory assessed by Barnes maze. They also had impaired hippocampus-dependent learning and memory in fear conditioning test. IL-1β in the hippocampus was increased at 6 h after isoflurane exposure. Isoflurane also increased activated caspase 3 in the hippocampus and decreased the neuronal density in the CA1 region. However, isoflurane did not change the amount of β-amyloid peptide in the cerebral cortex at 29 days after isoflurane exposure when cognitive impairment was present. These results suggest that isoflurane increases inflammatory cytokine expression and causes cell injury in the hippocampus, which may contribute to isoflurane-induced cognitive impairment in rats.
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Daowei
authors.initials: D
authors.lastname: Lin
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D003072:Cognition Disorders / Q000150:complications* / Q000473:pathology*; D003213:Conditioning, Psychological / Q000187:drug effects; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005239:Fear / Q000187:drug effects; D006624:Hippocampus / Q000473:pathology*; D053583:Interleukin-1beta / Q000378:metabolism; D007530:Isoflurane / Q000009:adverse effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018685:Anesthetics, Inhalation; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D007530:Isoflurane; D053148:Caspase 3