Dexmedetomidine renders a brain protection on hippocampal formation through inhibition of nNOS-NO signalling in endotoxin-induced shock rats

Xiong, Bin; Shi, Qiqing; Miao, Changhong

doi:10.3109/02699052.2014.888765

Cited by 10 publications

(8 citation statements)

References 25 publications

(29 reference statements)

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“…These dosages are at/under the lower levels of dexmedetomidine concentrations used in common adult rat models of neuronal damage [ 39 , 40 ] and the present data are not intended to demonstrate the evidence of an effective dose. However, our findings conform with different other animal studies which examined the neuroprotective capacity of dexmedetomidine [ 22 – 27 ]. Hyperoxia-exposed rats revealed an up to 5-fold increase in cell degeneration within the cortex and deep gray matter ( Figure 1(b) ), which has been demonstrated in previous studies [ 17 , 41 ].…”

Section: Discussionsupporting

confidence: 92%

“…Dexmedetomidine is a potent and highly selective agonist of α 2-receptors with sedative, anxiolytic, analgesic, and anesthetic properties [ 19 – 21 ]. In addition, it is generally reported that dexmedetomidine has neuroprotective effects in different animal models [ 22 – 27 ] and minimal side effects on the respiratory tract and the gastrointestinal function that minimizes the exposure to other narcotics and benzodiazepines [ 23 , 28 – 30 ]. Recent studies suggest the α 2-adrenoceptor agonist dexmedetomidine to attenuate anesthetic agent induced neuroapoptosis [ 26 , 31 , 32 ] and it appears for long term sedation as an alternative to midazolam and propofol [ 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

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Neuroprotective Effect of Dexmedetomidine on Hyperoxia-Induced Toxicity in the Neonatal Rat Brain

Sifringer

Haefen

Krain

et al. 2015

Oxidative Medicine and Cellular Longevity

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Dexmedetomidine is a highly selective agonist of α2-receptors with sedative, anxiolytic, analgesic, and anesthetic properties. Neuroprotective effects of dexmedetomidine have been reported in various brain injury models. In the present study, we investigated the effects of dexmedetomidine on neurodegeneration, oxidative stress markers, and inflammation following the induction of hyperoxia in neonatal rats. Six-day-old Wistar rats received different concentrations of dexmedetomidine (1, 5, or 10 µg/kg bodyweight) and were exposed to 80% oxygen for 24 h. Sex-matched littermates kept in room air and injected with normal saline or dexmedetomidine served as controls. Dexmedetomidine pretreatment significantly reduced hyperoxia-induced neurodegeneration in different brain regions of the neonatal rat. In addition, dexmedetomidine restored the reduced/oxidized glutathione ratio and attenuated the levels of malondialdehyde, a marker of lipid peroxidation, after exposure to high oxygen concentration. Moreover, administration of dexmedetomidine induced downregulation of IL-1β on mRNA and protein level in the developing rat brain. Dexmedetomidine provides protections against toxic oxygen induced neonatal brain injury which is likely associated with oxidative stress signaling and inflammatory cytokines. Our results suggest that dexmedetomidine may have a therapeutic potential since oxygen administration to neonates is sometimes inevitable.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effect of Dexmedetomidine on Hyperoxia-Induced Toxicity in the Neonatal Rat Brain

Sifringer

Haefen

Krain

et al. 2015

Oxidative Medicine and Cellular Longevity

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“…Besides, Dex reduced the release of glutamate and thus was considered to have neuroprotective effects [24]. In addition, it was generally reported that Dex had neuroprotective effects in different animal models due to its anti-oxidative damage effects [25][26][27]. This was similar to our results, in which Dex increased PC12 cell viability and decreased apoptosis, along with inhibited ROS formation to protect the cell from oxidative damage.…”

Section: Discussionsupporting

confidence: 91%

Dexmedetomidine protects PC12 cells from oxidative damage through regulation of miR-199a/HIF-1α

Yang

Kong

2020

Artificial Cells, Nanomedicine, and Biotechnology

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Background: Although dexmedetomidine (Dex) has a significant neuroprotective effect in various nerve-damage models, the exact mechanism of which Dex protects cells from oxidative damage is not fully clear. This article recommended the protective effect of Dex on oxidative damage in PC12 cells. Methods: The PC12 cells were incubated by hydrogen peroxide (H 2 O 2) for 24 h and pre-treated by Dex for 30 min. Cell viability, apoptosis, HIF-1a expression and ROS level were detected by CCK-8, apoptosis assay, Western blot and ROS assay, respectively. The miR-199a expression was tested by qRT-PCR. Targeting relationship between miR-199a and HIF-1a was performed by dual luciferase activity assay. The activation of PI3K/AKT/mTOR and Wnt/b-catenin pathways was tested by western blot. Results: Dex attenuated H 2 O 2-induced oxidative damage, including the decline of cell viability, the raise of apoptosis and the generation of ROS in PC12 cells by down-regulating miR-199a expression. Moreover, Dex up-regulated HIF-1a expression via decreasing miR-199a level in PC12 cells and miR-199a targeted the 3 0-UTR of HIF-1a. In addition, Dex activated PI3K/AKT/mTOR and Wnt/b-catenin pathways by declining miR-199a level. Conclusions: This article illustrated the protective effect of Dex on oxidative damage in PC12 cells. Furthermore, Dex prevented PC12 cells from oxidative injury through the regulation of miR-199a/ HIF-1a.

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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%

“…Liao et al (2014) reported that both JNK and P38 MAPK pathways participate in the protection by dexmedetomidine against isoflurane-induced neuroapoptosis in the hippocampus of neonatal rats. There have been studies reporting that dexmedetomidine renders brain protection in several brain injury models (Clancy et al, 2001;Schoeler et al, 2012;Degos et al, 2013;Xiong et al, 2014;Pan et al, 2016). Dexmedetomidine has also shown beneficial effects in other experimental models, for example by decreasing inflammatory mediators in endotoxininduced shock in rats (Taniguchi et al, 2004) or lipopolysaccha-ride-stimulated astrocytes (Zhang et al, 2014).…”

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 renders a brain protection on hippocampal formation through inhibition of nNOS-NO signalling in endotoxin-induced shock rats

Abstract: These results demonstrated that Dex exerted a brain protection on hippocampal formation through inhibition of the nNOS-NO signalling in ES rats and Dex may have a favourably therapeutic value in treating brain damage in patients with endotoxin shock.

Cited by 10 publications

References 25 publications

Neuroprotective Effect of Dexmedetomidine on Hyperoxia-Induced Toxicity in the Neonatal Rat Brain

Neuroprotective Effect of Dexmedetomidine on Hyperoxia-Induced Toxicity in the Neonatal Rat Brain

Dexmedetomidine protects PC12 cells from oxidative damage through regulation of miR-199a/HIF-1α

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

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