Dexmedetomidine provides neuroprotection: impact on ketamine‐induced neuroapoptosis in the developing rat brain

Duan, Xiaofeng; Li, Y.; Zhou, Changle; Huang, Liyi; Dong, Zhao

doi:10.1111/aas.12356

Cited by 90 publications

(77 citation statements)

References 19 publications

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“…In addition to studies of neonatal anesthetic exposure, a number of studies of fetal anesthetic exposure in rodents, sheep, and non-human primates have been published; neuroapoptosis and other neurodegenerative changes are described with fetal exposure to ketamine, propofol, volatile anesthetic agents, barbiturates, and benzodiazepines [19][20][21][22] .…”

Section: Anesthetic Neurotoxicity In Animal Models Of the Developing mentioning

confidence: 99%

“…Since the Sanders paper in 2009, there have been 9 additional published studies in fetal or neonatal animal models assessing dexmedetomidine's effect on neuroapoptosis. Of these 10 total studies, 8 demonstrate no neuroapoptosis, and in all 3 studies that conducted later neurobehavioral testing in surviving animals, dexmedetomidine ameliorated the deficits associated with isoflurane administration [19][20][21][22][36][37][38][39][40] ( Table 2 ). In a study by Pancaro et al [40] , dexmedetomidine at very high doses did result in neuroapoptosis in the sensory cortex and the thalamus.…”

Section: Effect Of Anesthesia On the Developing Brainmentioning

confidence: 99%

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Effect of Anesthesia on the Developing Brain: Infant and Fetus

2017

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Section: Anesthetic Neurotoxicity In Animal Models Of the Developing mentioning

confidence: 99%

Section: Effect Of Anesthesia On the Developing Brainmentioning

confidence: 99%

Effect of Anesthesia on the Developing Brain: Infant and Fetus

2017

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“…In recent years, increasing basic and clinical studies have proved that DEX protected against different types of organs. Duan et al (10) reported that DEX was not neurotoxic and attenuated neuroapoptosis; other studies indicated that DEX application following cardiac surgery was associated with a lower incidence of atrial arrhythmias (11); Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats (12,13). However, mechanisms of the DEX protective effects are unclear, particularly for renal protection.…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats

et al. 2015

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Abstract. Approximately 42% of patients with sepsis undergo acute kidney injury (AKI), which evidently influences patient survival. However, effective therapy strategies are lacking, thus, the present study investigated the protective effects of dexmedetomidine (DEX), a highly selective α-2 adrenoceptor agonist, in rat sepsis models. Rat sepsis models were generated through lipopolysaccharide injection (LPS; 5 mg/kg) in the tail vein. Rats were pretreated with DEX (10 µg/kg) 10 min before LPS injection to observe its protective effects. Of note, a unique α-2-adrenergic receptor antagonist, yohimbine (YOH; 1 mg/kg, intraperitoneally), was also used to antagonize the protective effects of DEX 30 min before DEX exposure. Thirty-two male Sprague Dawley rats were randomly divided into the Sham, LPS, DEX + LPS and YOH + DEX + LPS groups (n=8/group). All the rats were sacrificed 4 h later to observe the pathological changes of renal tissue, including plasma creatinine (Cr), blood urea nitrogen (BUN), kidney injury molecule-1 (KIM-1) and high mobility group protein 1 (HMGB-1) expression. Interleukin 6 (IL-6), IL-18 and tumor necrosis factor α (TNF-α) were all determined to examine the mechanisms of LPS-induced AKI relative to inflammatory reaction. The results indicated that AKI induced by LPS was serious. Renal pathological injury, plasma Cr, BUN, IL-6, IL-18 and TNF-α were all evidently increased in varying degrees. KIM-1 and HMGB-1 expression was upregulated in the LPS group (P<0.05 vs. Sham group). However, when rats were pretreated with DEX, AKI induced by LPS was decreased significantly. Renal pathological injury, plasma Cr, BUN, IL-6, IL-18, TNF-α, and KIM-1 and HMGB-1 expression were all reduced (P<0.05 vs. LPS group). In addition, exposure of the α-2-adrenergic receptor antagonist, YOH, eliminated this reduction. In conclusion, DEX protected against sepsis-induced AKI through depressing the inflammatory reaction, mechanisms of which may be associated with α-2 receptors inhibition. IntroductionSepsis, also called septicemia, is a serious complication of patients undergoing pathogen infection, trauma, burn, hypoxia, reperfusion injury and surgery, which could affect myocardial contractility, decreased organ oxygen uptake capacity, and can lead to septic shock and multiple organ dysfunction syndrome. This state is called systemic inflammatory response syndrome (1,2). The incidence of sepsis is extremely high in the intensive care unit (ICU), with a mortality of ≤40-80%. As reported, the kidney is one of the most susceptible target organs of sepsis (3). Approximately 50% of patients suffer from acute kidney injury (AKI) caused by sepsis. Notably, mortality of these patients is as high as 70% (4,5). However, the mechanisms of sepsis-induced AKI remain unclear and effective therapy strategies are also lacking.Inflammatory factors, such as interleukin 6 (IL-6), IL-18 and tumor necrosis factor α (TNF-α), play an important role in the pathological and physiological process, particularly IL-18. As recently reported, IL-1...

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“…Since the antagonist atipamezole of the α2-adrenoceptor only partly reversed the neuroprotective effects of dexmedetomidine on neurotoxicity in rats induced by isoflurane, there may be other mechanisms. Several pathways have been reportedly involved in the neuroprotection of dexmedetomidine (Cai et al, 2014;Duan et al, 2014;Liao et al, 2014;Xiong et al, 2014). Li et al (2014) found that dexmedetomidine pretreatment dose-dependently inhibited isofluraneinduced neuroapoptosis by preserving the PI3K/Akt pathway in the hippocampus in neonatal rats.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotection of dexmedetomidine against propofol-induced neuroapoptosis partly mediated by PI3K/Akt pathway in hippocampal neurons of fetal rat

Ning

Weixia

et al. 2017

J. Zhejiang Univ. Sci. B

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Abstract:The aim was to investigate how the PI3K/Akt pathway is involved in the protection of dexmedetomidine against propofol. The hippocampal neurons from fetal rats were separated and cultured in a neurobasal medium. Cell viability was assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Then neurons were pretreated with different concentrations of dexmedetomidine before 100 μmol/L propofol was added. Akt, phospho-Akt (p-Akt), Bad, phospho-Bad (p-Bad), and Bcl-xL were detected by Western blot. Also, neurons were pretreated with dexmedetomidine alone or given the inhibitor LY294002 before dexmedetomidine pretreatment, and then propofol was added for 3 h. The results demonstrated that propofol decreased the cell viability and the expression of p-Akt and p-Bad proteins, increased the level of Bad, and reduced the ratio of Bcl-xL/Bad. Dexmedetomidine pretreatment could reverse these effects. The enhancement of p-Akt and p-Bad induced by dexmedetomidine was prevented by LY294002. These results showed that dexmedetomidine potently protected the developing neuron and this protection may be partly mediated by the PI3K/Akt pathway.

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Dexmedetomidine provides neuroprotection: impact on ketamine‐induced neuroapoptosis in the developing rat brain

Abstract: In conclusion, ketamine caused neuroapoptosis and impaired brain functions in the developing rat brain which can be effectively attenuated by dexmedetomidine. Dexmedetomidine alone was not neurotoxic to the developing brain.

Cited by 90 publications

References 19 publications

Effect of Anesthesia on the Developing Brain: Infant and Fetus

Effect of Anesthesia on the Developing Brain: Infant and Fetus

Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats

Neuroprotection of dexmedetomidine against propofol-induced neuroapoptosis partly mediated by PI3K/Akt pathway in hippocampal neurons of fetal rat

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