Lidocaine attenuates cognitive impairment after isoflurane anesthesia in old rats

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 2 h had significant learning and memory impairments assessed at 2-4 weeks after isoflurane exposure. These isoflurane effects were attenuated by intravenous lidocaine (1.5 mg/kg as a bolus and then 2 mg/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 beta-amyloid peptide, total tau and phospho-tau in the cerebral cortex as well as interleukin-1 beta and tumor necrosis factor-a 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. (C) 2011 Elsevier B.V. All rights reserved.