Resveratrol-loaded nanoemulsion prevents cognitive decline after abdominal surgery in aged rats

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.

The Investigation of Hippocampus-Dependent Cognitive Decline Induced by Anesthesia/Surgery in Mice Through Integrated Behavioral Z-Scoring

“…Hovens et al (2014) reported that exploratory behavior, but not learning and memory, was significantly correlated with plasma IL-6 levels 24 h following abdominal surgery, and microglial activation in hippocampal CA1 was significantly correlated with the performance of OF, FC, and Y-maze at 43 days after surgery (Hovens et al, 2013). In addition, other studies also found that there was an inverse relationship between hippocampal TNF-α and IL-1β levels, and NOR performance 7 days after abdominal surgery (Kawano et al, 2015;Locatelli et al, 2018). The reason for the negative results of the correlation analysis in the present study was largely due to the fact that hippocampal pro-inflammatory cytokines had almost decreased to baseline after the behavioral tests was completed (Figure 9A), which was further proved by hippocampal TNF-α, IL-6, and IL-1β mRNA levels that decreased to around control levels on day 3 and/or day 7 following surgery ( Figure 10).…”

“…The results showed that there were no significant differences in the three pro-inflammatory cytokines between groups (Figure 9A). Some studies reported that there was an inverse relationship between levels of proinflammatory cytokines and behavioral performance after surgery (Kawano et al, 2015;Locatelli et al, 2018). Accordingly, we decided to investigate the correlation between three hippocampal cytokine levels and the integrated memory Z-scores by combinations of different behavioral tests.…”

Baicalin Ameliorates Cognitive Impairment and Protects Microglia from LPS-Induced Neuroinflammation via the SIRT1/HMGB1 Pathway

“…Decreased expression levels of SIRT1 have been observed in the hippocampus of aged dNCR model mice [ 13 ]. dNCR model mice respond to therapies by upregulating SIRT1 expression in the hippocampus, as shown by a neuroprotective treatment of aged mice with SIRT1 activators [ 14 , 15 ]. Recent reports have shown that SIRT1 is involved in protein quality control, as SIRT1 suppressed aggregation of tau proteins [ 16 ] and HMGB1 transcription [ 17 ] by direct deacetylation regulation.…”

Natural polyphenols in preclinical models of epilepsy

“…SIRT1 represents a class III lysine deacetylase that is expressed in neuronal cells and known to preserve the mitochondrial function (Houtkooper, Pirinen, & Auwerx, ). The neuroprotective action of resveratrol has been shown to be through SIRT 1 activation (Locatelli et al, ). Sirtinol, a specific SIRT1 inhibitor, could inhibit this effect (Locatelli et al, ).…”

“…The neuroprotective action of resveratrol has been shown to be through SIRT 1 activation (Locatelli et al, ). Sirtinol, a specific SIRT1 inhibitor, could inhibit this effect (Locatelli et al, ). SIRT1 may interact with PGC‐1α and therefore performs a significant role in mitochondrial biogenesis (Nemoto, Fergusson, & Finkel, ).…”