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Dexmedetomidine provides cortical neuroprotection: impact on anaesthetic-induced neuroapoptosis in the rat developing brain
Sanders, R. D.1; Sun, P.1; Patel, S.1; Li, M.2; Maze, M.1; Ma, D.1
刊名ACTA ANAESTHESIOLOGICA SCANDINAVICA
2010-07-01
DOI10.1111/j.1399-6576.2009.02177.x
54期:6页:710-716
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Anesthesiology
研究领域[WOS]Anesthesiology
关键词[WOS]INDUCED NEURONAL APOPTOSIS ; STAUROSPORINE ; PROTECTS ; AGONISTS
英文摘要

Background

Recent evidence has demonstrated the anti-apoptotic of dexmedetomidine in different brain injury models. Herein, we investigated whether dexmedetomidine could directly protect against cortical injury in vitro and in vivo.

Methods

Apoptosis was induced by staurosporine or wortmannin treatment in cortical neuronal cultures in vitro or by 6 h of isoflurane (0.75%) administration to post-natal day 7 rat pups in vivo. Dexmedetomidine was then applied in escalating doses to assess the neuroprotective potential of this agent. Cell survival was quantified using an MTT assay in vitro and in vivo apoptosis was assessed using cleaved caspase-3 immunohistochemistry. Cortical Western blots were conducted for the cellular survival proteins Bcl-2 and phosphorylated extracellular signal-regulated protein kinase (pERK)1 and 2.

Results

In vitro dexmedetomidine dose-dependently prevented both staurosporine- and wortmannin-induced injury in cortical neuronal cultures, indicating that dexmedetomidine can prevent apoptosis when applied directly. In vivo isoflurane induced cortical neuroapoptosis compared with air (327 +/- 80 vs. 34 +/- 9 caspase-3-positive neurons; P < 0.05). Dexmedetomidine inhibited isoflurane-induced caspase-3 expression (P < 0.05), although the protection achieved did not completely attenuate the isoflurane injury (P < 0.05 vs. air). Isoflurane treatment decreased Bcl-2 and pERK protein expression relative to air, an effect reversed by dexmedetomidine treatment.

Conclusions

Dexmedetomidine prevents cortical apoptosis in vitro and in vivo. However, using higher doses of dexmedetomidine does not further increase protection against isoflurane injury in the cortex than previously observed.

语种英语
WOS记录号WOS:000278292400007
资助机构European Society of Anaesthesiology, Chelsea and Westminster Healthcare NHS Trust ; Westminster Medical School Research Trust
引用统计
被引频次:128[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62048
专题北京大学第三临床医学院_麻醉科
作者单位1.Univ London Imperial Coll Sci Technol & Med, Chelsea & Westminster Hosp, Magill Dept Anaesthet Intens Care & Pain Med, London SW10 9NH, England
2.Peking Univ, Hosp 3, Dept Anesthesiol, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Sanders, R. D.,Sun, P.,Patel, S.,et al. Dexmedetomidine provides cortical neuroprotection: impact on anaesthetic-induced neuroapoptosis in the rat developing brain[J]. ACTA ANAESTHESIOLOGICA SCANDINAVICA,2010,54(6):710-716.
APA Sanders, R. D.,Sun, P.,Patel, S.,Li, M.,Maze, M.,&Ma, D..(2010).Dexmedetomidine provides cortical neuroprotection: impact on anaesthetic-induced neuroapoptosis in the rat developing brain.ACTA ANAESTHESIOLOGICA SCANDINAVICA,54(6),710-716.
MLA Sanders, R. D.,et al."Dexmedetomidine provides cortical neuroprotection: impact on anaesthetic-induced neuroapoptosis in the rat developing brain".ACTA ANAESTHESIOLOGICA SCANDINAVICA 54.6(2010):710-716.
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