Abstract:
: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.
journal_name
J Pharmacol Scijournal_title
Journal of pharmacological sciencesauthors
Locatelli FM,Kawano T,Iwata H,Aoyama B,Eguchi S,Nishigaki A,Yamanaka D,Tateiwa H,Shigematsu-Locatelli M,Yokoyama Mdoi
10.1016/j.jphs.2018.08.006subject
Has Abstractpub_date
2018-08-01 00:00:00pages
395-402issue
4eissn
1347-8613issn
1347-8648pii
S1347-8613(18)30155-5journal_volume
137pub_type
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