Dexmedetomidine protects rats from postoperative cognitive dysfunction via regulating the GABA_BR‐mediated cAMP‐PKA‐CREB signaling pathway

Abstract

This work attempts to discuss whether dexmedetomidine (Dex) can protect rats from postoperative cognitive dysfunction (POCD) through regulating the γ‐aminobutyric acid‐B receptor (GABABR)‐mediated cyclic adenosine monophosphate (cAMP) – protein kinase A (PKA) – cAMP‐response element binding (cAMP‐PKA‐CREB) signaling pathway. Sprague‐Dawley rats were divided into a non‐surgical group (Control), a surgical group (Model), a surgical group treated with Dex (Model + Dex), a surgical group treated with GABABR antagonist (Model + CGP 35348) and a surgical group treated with Dex and GABABR agonist (Model + Dex + Baclofen). Cognitive and memory functions were evaluated by Y‐maze test and open‐field test. The neuronal morphology of the hippocampus was observed by hematoxylin and eosin staining and neuronal apoptosis was by terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick‐end labeling method. Inflammatory factors and cAMP levels were detected by enzyme‐linked immunosorbent assay while expressions of GABABR and PKA‐CREB pathway‐related molecules by Western blot. Compared with control rats, the model rats exhibited reduced alternation rates with a prolonged time spent in the central zone; meanwhile, levels of tumor necrosis factor‐α and interleukin‐1β and the apoptotic index, as well as GABABR1 and GABABR2 expressions were increased in the model rats, but the cAMP‐PKA‐CREB pathway was inhibited (all P < 0.05). When treated with either Dex or CGP 35348, the surgical rats displayed an opposite tendency concerning the above factors as compared to the model rats (all P < 0.05). Furthermore, Baclofen, the agonist of GABABR, could reverse the protective effect of Dex against POCD in rats. Dex protects rats from POCD possibly via suppressing GABABR to up‐regulate the cAMP‐PKA‐CREB signaling pathway, thereby alleviating the hippocampal inflammation caused by surgical trauma.

The Effects of Dexmedetomidine in a Rat Model of Sepsis-Induced Lung Injury are Mediated Through the Adenosine Monophosphate-Activated Protein Kinase (AMPK)/Silent Information Regulator 1 (SIRT1) Pathway

“…In the present study, dexmedetomidine significantly reduced the levels of IL-1b and TNF-a and increased the levels of IL-10 in lung tissues in the rat model of sepsis, and significantly reduced sepsis-induced lung injury. These findings are supported by those from a previous animal model study reported by Zhu et al [15] who found that dexmedetomidine significantly reduced the inflammatory response in the lung, and inhibited the release of inflammatory cytokines, to reduce lung injury. .…”

Dexmedetomidine protects aged rats from postoperative cognitive dysfunction by alleviating hippocampal inflammation

“…The total number of arms a rat passes in the Y-maze test is considered to be an index reflecting the exercise ability of the rats (17). The number of rats passing alternative arms at each time point is shown in Fig.…”

“…Dexmedetomidine (10 and 30 µg/kg; Nanjing Chemlin Chemical Industry Co., Ltd.) was intraperitoneally injected 1 h after surgery for the low- and high-dose anesthesia groups, respectively. The dose selection was based on previous studies (17,18). All rats received an intramuscular injection of penicillin (200,000 units) daily for 3 days after surgery to prevent infection.…”

<p>Dexmedetomidine Attenuates Neuroinflammation In LPS-Stimulated BV2 Microglia Cells Through Upregulation Of miR-340</p>

“…Previous study found that Dex could decrease the duration of mechanical ventilation and the morbidity of POCD 16,17. In addition, Dex could alleviate POCD in rats via regulating cAMP signaling pathway 18. Moreover, Li et al found that Dex decreased the production of inflammatory factors and reduced postoperative recurrent rate in patients with POCD 19…”