Isoflurane causes neocortical but not hippocampal-dependent memory impairment in mice.

BACKGROUND: The aim of this study is to investigate the effect of general anaesthesia induced by isoflurane with buprenorphine on hippocampus-dependent and neocortex-dependent memory, respectively, in mice, and in addition, to compare the effects of such anaesthesia on these memory processes with the effects induced by lipopolysaccharide (LPS) administration on the same memory processes. METHODS: To assess hippocampus-dependent memory, isoflurane (for 15 min) after buprenorphine injection, or LPS 100 µg/kg (intraperitoneally) was administered 24 h before or after fear conditioning. The effect of these treatments on hippocampus-dependent memory was assessed using contextual fear-conditioning tasks at day 4. To assess neocortex-dependent memory, isoflurane anaesthesia or LPS was given 72 h after contextual fear conditioning. Neocortex-dependent memory assessment was performed at day 32. RESULTS: Unlike LPS injection, isoflurane with buprenorphine-induced anaesthesia does not impair freezing responses in hippocampus-dependent fear-conditioning memory tasks. On anterograde amnesia assessment: 49.67 ± 6.87% for the anaesthesia group and 54.5 ± 4.12% for the control group. On retrograde amnesia assessment: 47.16 ± 8.71% for the anaesthesia group and 54.5 ± 4.12% for control group; P > 0.05. Thus, neither isoflurane nor buprenorphine impair hippocampus-dependent memory. However, on the neocortex-dependent memory task, both isoflurane-induced anaesthesia and LPS-induced inflammation result in reduced freezing responses: 62.13 ± 5.80% for the anaesthesia group, 74.63 ± 5.69% for the LPS group, and 81.75 ± 3.26% for the control group; P < 0.05 compared with control group. CONCLUSION: General anaesthesia induced by isoflurane with buprenorphine may result in impairment of neocortex-dependent memory in mouse. However, general anaesthesia so induced does not impair hippocampus-dependent memory in mouse in our experimental conditions.

Peripheral orthopaedic surgery down-regulates hippocampal brain-derived neurotrophic factor and impairs remote memory in mouse.

Peripheral orthopaedic surgery induces a profound inflammatory response. This includes a substantial increase in cytokines and, especially, in the level of interleukin (IL)-1ß in the hippocampus, which has been shown to impair hippocampal-dependent memory in mice. We have employed two tests of contextual remote memory to demonstrate that the inflammatory response to surgical insult in mice also results in impairment of remote memory associated with prefrontal cortex (PFC). We have also found that, under the conditions presented in the social interaction test, peripheral orthopaedic surgery does not increase anxiety-like behaviour in our animal model. Although such surgery induces an increase in the level of IL-1ß in the hippocampus, it fails to do so in the PFC. Peripheral orthopaedic surgery also results in a reduction in the level of hippocampal brain-derived neurotrophic factor (BDNF) and this may contribute, in part, to the memory impairment found after such surgery. Our data suggest that a reduction in the level of hippocampal BDNF and an increase in the level of hippocampal IL-1ß following surgery may affect the transference of fear memory in the mouse brain.

Sensitization of the transient receptor potential vanilloid type 1 ion channel by isoflurane or sevoflurane does not result in extracellular signal-regulated kinase 1/2 activation in rat spinal dorsal horn neurons.

Clinically relevant concentrations of isoflurane or sevoflurane sensitize transient receptor potential vanilloid type 1 to several of its activators, including capsaicin. It has, moreover, been suggested these volatile general anaesthetics may augment nociceptive signalling arising from surgical procedures and thereby contribute to post-operative pain. To investigate this suggestion, we have studied intraplantar capsaicin injection-induced phosphorylation of extracellular signal-regulated kinase 1/2 in spinal dorsal horn neurons (which is a recognized marker of spinal nociceptive processing) in rat during isoflurane or sevoflurane anaesthesia after 60 min under anaesthesia. Control animals were anaesthetized with pentobarbital (which of itself does not activate extracellular signal-regulated kinase 1/2 in spinal dorsal horn neurons). Unilateral intraplantar capsaicin injection in control animals evoked extracellular signal-regulated kinase 1/2 phosphorylation in a group of neurons in lamina I and lamina II of the ipsilateral spinal dorsal horn in a somatotopically appropriate area. In contrast, both anaesthetic gases (given for 60 min and without subsequent capsaicin injection) induced extracellular signal-regulated kinase 1/2 activation in a different group of mainly lamina I neurons bilaterally. The total number of spinal dorsal horn neurons labelled on the ipliateral side following capsaicin injection into the isoflurane-, or sevoflurane-, anaesthetized animals was significantly less than that produced by capsaicin alone. Further, capsaicin injection into isoflurane-, or sevoflurane-, anaesthetized animals reduced extracellular signal-regulated kinase 1/2 phosphorylation induced by the gases alone on both sides. These findings do not support the suggestion that isoflurane-, or sevoflurane-, induced sensitization of transient receptor potential vanilloid type 1 by capsaicin, or other agonist, is translated into induction of spinal nociceptive processing and consequential pain sensation.