Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 137, Issue 4, Pages 395-402Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2018.08.006
Keywords
Resveratrol; Neuroinflammation; Postoperative cognitive dysfunction; Microglia
Categories
Funding
- Japan Society for the Promotion of Science, Tokyo, Japan [15K10538]
- Grants-in-Aid for Scientific Research [15K10538] Funding Source: KAKEN
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The maladaptive response of aged microglia to surgery and consequent neuroinflammation plays a key pathogenic role in postoperative cognitive dysfunction (POCD). Here, we assessed the preventive effect of resveratrol (RESV) for POCD in aged rats. The emulsified form of RESV (e-RESV) was selected to improve its oral and brain bioavailability. Animals were assigned to one of four groups: e-RESV (80 mg/kg) versus vehicle treatment by abdominal surgery versus isoflurane anesthesia alone (n = 8 in each group). The dose-dependent effects of e-RESV were also assessed in dose range of 0-60 mg/kg. Either vehicle or e-RESV was administered intragastrically 24 h before surgery. Seven days after procedure, cognitive function was evaluated using a novel object recognition test, followed by measurement of hippocampal pro-inflammatory cytokine levels. Our results showed that pre-treatment with e-RESV attenuated the surgery-induced cognitive impairment and related hippocampal neuroinflammation at 40 mg/kg or higher doses. Additionally, the ex-vivo experiments revealed that the preemptive e-RESV regimen reduced the hippocampal microglial immune reactivity to lipopolysaccharide. Furthermore, e-RESV induced neuroprotective benefits were inhibited by the concomitant administration of sirtinol, a specific SIRT1 inhibitor. Our findings imply the preventive potential of e-RESV for POCD via the SIRT1 signaling pathway. (c) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.
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