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.
Highlights
Perioperative neurocognitive disorders (PNDs) are very common cognitive impairments in older patients who have undergone surgery with anesthesia [1]
Acetate suppressed inflammation in lipopolysaccharide-treated BV2 microglial cells, but not when G protein-coupled receptor 43 (GPR43) was silenced. These results suggest that acetate may bind to GPR43, thereby inhibiting microglial activity, suppressing neuroinflammation, and preventing memory deficits
The percentage of time spent in the target quadrant, the distance traveled in the target quadrant and the number of platform crossings were all notably lower in the surgery group than in the normal group on postoperative day 3 (POD 3) and POD 7, signifying that the surgery had evoked cognitive deficits
Summary
Perioperative neurocognitive disorders (PNDs) are very common cognitive impairments in older patients who have undergone surgery with anesthesia [1]. Surgery can trigger acute systemic inflammation, followed by neuroinflammation and synaptic dysfunction, which can lead to hippocampus-dependent cognitive deficits [4,5,6]. The activation of microglia may induce the production of inflammatory proteins such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) via the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, resulting in neuroinflammation and cognitive deficits [11, 12]. Neurons are susceptible to these active substances, which contribute to oxidative stress and impair neurocognitive function [13, 14]. The targeted inhibition of microglial activity may improve neurocognitive function by suppressing neuroinflammation and oxidative stress
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