Dexmedetomidine Ameliorated Cognitive Dysfunction Induced by Intestinal Ischemia Reperfusion in Mice with Possible Relation to the Anti-inflammatory Effect Through the Locus Coeruleus Norepinephrine System

Abstract

Cognitive impairment is a common central nervous system complication that occurs following surgery or organs damage outside the nervous system. Neuroinflammation plays a key role in the molecular mechanisms of cognitive impairment. Dexmedetomidine alleviates neuroinflammation and reduces cognitive dysfunction incidence; however, the mechanism by which dexmedetomidine alleviates cognitive dysfunction remains unclear. This study evaluated the effect of dexmedetomidine on attenuation of early cognitive impairment induced by intestinal ischemia–reperfusion in mice and examined whether the locus coeruleus norepinephrine (LCNE) system participates in the anti-inflammatory effect of dexmedetomidine. The superior mesenteric artery was clamped for 45 min to induce intestinal ischemia reperfusion injury. Dexmedetomidine alone or combined with DSP-4, a selective locus coeruleus noradrenergic neurotoxin, was used for pretreatment. Postoperative cognition was assessed using the Morris water maze. Serum and hippocampal levels of IL-1β, TNF-α, norepinephrine (NE), and malondialdehyde (MDA) were assessed by enzyme-linked immunosorbent assay. Immunofluorescence, immunohistochemistry, and hematoxylin and eosin staining were used to evaluate the expression of tyrosine hydroxylase (TH) in the locus coeruleus, hippocampal microglia, and intestinal injury. Pretreatment with dexmedetomidine alleviated intestinal injury and decreased the serum and hippocampal levels of NE, IL-1β, TNF-α, and MDA at 24 h after intestinal ischemia reperfusion, decreased TH-positive neurons in the locus coeruleus, and ameliorated cognitive impairment. Similarly, DSP-4 pre-treatment alleviated neuroinflammation and improved cognitive function. Furthermore, α2-adrenergic receptor antagonist atipamezole or yohimbine administration diminished the neuroprotective effects and improved cognitive function with dexmedetomidine. Therefore, dexmedetomidine attenuated early cognitive dysfunction induced by intestinal ischemia–reperfusion injury in mice, which may be related to its anti-inflammatory effects through the LCNE system.

Attenuation of intestinal ischemia-reperfusion-injury by anesthetics: a potentially protective effect of anesthetic management in experimental studies

“…Some studies proved mucosal mast cell (IMMC) activation is critical in intestinal IRI by secreting many mediators to induce intestinal epithelial injury and integrity disruption. Propofol preconditioning can suppress IMMC activation, and it can explain why propofol can attenuate Intestinal IRI, restore intestinal epithelial cell integrity, and prevent intestinal IRI-induced lung injury in rodents and even pigs from other perspectives ( Zhao et al, 2014 ; Gan et al, 2015 ; Bian et al, 2021 ; Li et al, 2022a ). The above findings showed propofol may provide a meaningful anesthetic management regimen for preventing intestinal IRI and organ injury following major surgery and is worthy of a further clinical study to examine the clinical significance.…”