title: Lidocaine attenuates cognitive impairment after isoflurane anesthesia in old rats.
abstract: Post-operative cognitive dysfunction (POCD) is a clinical phenomenon that has drawn significant attention from the public and scientific community. Age is a risk factor for POCD. However, the contribution of general anesthesia/anesthetics to POCD and the underlying neuropathology are not clear. Here, we showed that 18-month-old male Fisher 344 rats exposed to 1.2% isoflurane, a general anesthetic, for 2h had significant learning and memory impairments assessed at 2-4 weeks after isoflurane exposure. These isoflurane effects were attenuated by intravenous lidocaine (1.5mg/kg as a bolus and then 2mg/kg/h during isoflurane exposure), a local anesthetic that has neuroprotective effect. Exposure to isoflurane or isoflurane plus lidocaine did not change the neuronal and synaptic density as well as the expression of NeuN (a neuronal protein), drebrin (a dendritic spine protein), synaptophysin (a synaptic protein), activated caspase 3 and caspase-activated DNase in the hippocampus at 29 days after isoflurane exposure when cognitive impairment was present. Isoflurane and lidocaine did not affect the amount of β-amyloid peptide, total tau and phospho-tau in the cerebral cortex as well as interleukin-1β and tumor necrosis factor-α in the hippocampus at 29 days after isoflurane exposure. Thus, isoflurane induces learning and memory impairment in old rats. Lidocaine attenuates these isoflurane effects. Isoflurane may not cause long-lasting neuropathological changes.
authors.affiliation: Department of Anesthesiology, University of Virginia, 1 Hospital Drive, Charlottesville, VA 22908, USA.
authors.forename: Daowei
authors.initials: D
authors.lastname: Lin
authors.forename: Lin
authors.initials: L
authors.lastname: Cao
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.forename: Jiejie
authors.initials: J
authors.lastname: Li
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Washington
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000375:Aging / Q000187:drug effects; D016229:Amyloid beta-Peptides / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000779:Anesthetics, Local / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D003213:Conditioning, Psychological / Q000187:drug effects; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay; D005239:Fear / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D053583:Interleukin-1beta / Q000378:metabolism; D007530:Isoflurane / Q000009:adverse effects*; D008012:Lidocaine / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D010446:Peptide Fragments / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013569:Synapses / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018685:Anesthetics, Inhalation; D000779:Anesthetics, Local; D053583:Interleukin-1beta; D010446:Peptide Fragments; D016708:Synaptophysin; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); D008012:Lidocaine; D007530:Isoflurane; D010751:Phosphopyruvate Hydratase