Acetate attenuates perioperative neurocognitive disorders in aged mice

Abstract

Perioperative neurocognitive disorders are common in elderly patients who have undergone surgical procedures. Neuroinflammation induced by microglial activation is a hallmark of these neurological disorders. Acetate can suppress inflammation in the context of inflammatory diseases. We employed an exploratory laparotomy model with isoflurane anesthesia to study the effects of acetate on perioperative neurocognitive disorders in aged mice. Neurocognitive function was assessed with open-field tests and Morris water maze tests 3 or 7 days post-surgery. Acetate ameliorated the surgery-induced cognitive deficits of aged mice and inhibited the activation of IBA-1, a marker of microglial activity. Acetate also reduced expression of inflammatory proteins (tumor necrosis factor-α, interleukin-1β and interleukin-6), oxidative stress factors (NADPH oxidase 2, inducible nitric oxide synthase and reactive oxygen species), and signaling molecules (nuclear factor kappa B and mitogen-activated protein kinase) in the hippocampus. BV2 microglial cells were used to verify the anti-inflammatory effects of acetate in vitro. Acetate suppressed inflammation in lipopolysaccharide-treated BV2 microglial cells, but not when GPR43 was silenced. These results suggest that acetate may bind to GPR43, thereby inhibiting microglial activity, suppressing neuroinflammation, and preventing memory deficits. This makes acetate is a promising therapeutic for surgery-induced neurocognitive disorders and neuroinflammation.

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“…The cylinder test was performed according to the standard protocol. 55 , 56 , 57 , 58 A cylinder made of thick glass was used to assess forepaw asymmetry. The mouse was placed in the glass cylinder for 10 min, and the video was recorded from the side.…”

Elamipretide Attenuates Pyroptosis and Perioperative Neurocognitive Disorders in Aged Mice

“…Exploratory laparotomy was performed under aseptic conditions with isoflurane anesthesia, as described in previous studies (Qiu et al, 2020 ; Wen et al, 2020 ). This model has been used in studies investigating both postoperative delirium (Peng et al, 2016 ; Lu et al, 2020 ) and postoperative cognitive dysfunction (Kawano et al, 2015 ; Qiu et al, 2020 ), and is referred to as a model for PND in this study, according to the nomenclature recently adopted in major anesthesiology journals.…”

“…In the present study, we used a mouse model involving exploratory laparotomy under isoflurane anesthesia to mimic clinical human abdominal surgery. This preclinical model has been shown to induce neuroinflammation and cognitive deficits and has been widely used to investigate the molecular basis of PND and to test potential therapeutic strategies (Qiu et al, 2020 ; Wen et al, 2020 ). We hypothesized that: (1) anesthesia and surgery would cause mitochondrial dysfunction and trigger the activation of NLRP3 inflammasome-caspase-1 dependent pyroptosis in the hippocampus in aged mice, thus contributing to PND pathogenesis; and (2) administration of elamipretide would protect against surgery-induced cognitive deficits by attenuating mitochondrial dysfunction and neuronal pyroptosis.…”

Senkyunolide I Protects Against Sepsis-associated Encephalopathy by Attenuating Sleep Deprivation in a Murine Model of Cecal Ligation and Puncture

“…MAPKs signaling pathway and NF-κB signaling pathway are involved in various in ammatory diseases and also contribute to the production of TNF-α, IL-1β, IL-6, hence reducing neuronal plasticity and neurogenesis (22). These in ammatory signaling pathways were also demonstrated to be activated in the process of sepsis-associated encephalopathy (23,24).…”