HSP27 protects the blood-brain barrier against ischemia-induced loss of integrity.
HSP27 protects the blood-brain barrier against ischemia-induced loss of integrity.
复制标题
HSP27可保护血脑屏障免受缺血诱导的完整性丧失。
DOI：
10.2174/1871527311312030006
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发表时间：
2013-05-01
期刊：
影响因子：
--
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Leak RK;Zhang L;Stetler RA;Weng Z;Li P;Atkins GB;Gao Y;Chen J
中风患者血脑屏障（BBB）完整性的丧失引发了一系列破坏性事件，包括血液传播分子、水和炎性细胞外渗到脑实质深处。因此，重要的是要确定的机制，血脑屏障的完整性可以保持在面对缺血性损伤的实验性中风。我们以前证明，在遗传学上保守的小热休克蛋白27（HSP 27）保护对短暂的大脑中动脉闭塞（tMCAO）。在这里，我们表明，热休克蛋白27转基因过表达也保持了BBB的完整性，在小鼠进行tMCAO。在转基因小鼠中，tMCAO后内源性IgG抗体和外源性FITC-白蛋白外渗到脑中的情况减少，脑总含水量也减少。HSP 27过表达可使微血管壁TUNEL阳性表达消失。转基因也表现出较少的损失微血管蛋白tMCAO。值得注意的是，原代内皮细胞培养物被拯救从氧-葡萄糖剥夺（OGD）的慢病毒HSP 27过表达根据四个活力测定，支持对这种细胞类型的直接影响。最后，HSP 27过表达减少了脑中中性粒细胞的出现，并抑制了五种细胞因子的分泌。这些发现揭示了HSP 27在减轻缺血/再灌注损伤中的新作用-维持BBB完整性。野生型动物缺血后HSP 27的内源性上调可能发挥类似的保护作用，值得进一步研究。通过合理的药物设计外源性增强HSP 27可能会导致未来针对一系列损伤的治疗，包括但不限于脑血管系统中的有害破坏。
Loss of integrity of the blood-brain barrier (BBB) in stroke victims initiates a devastating cascade of events including extravasation of blood-borne molecules, water, and inflammatory cells deep into brain parenchyma. Thus, it is important to identify mechanisms by which BBB integrity can be maintained in the face of ischemic injury in experimental stroke. We previously demonstrated that the phylogenetically conserved small heat shock protein 27 (HSP27) protects against transient middle cerebral artery occlusion (tMCAO). Here we show that HSP27 transgenic overexpression also maintains the integrity of the BBB in mice subjected to tMCAO. Extravasation of endogenous IgG antibodies and exogenous FITC-albumin into the brain following tMCAO was reduced in transgenic mice, as was total brain water content. HSP27 overexpression abolished the appearance of TUNEL-positive profiles in microvessel walls. Transgenics also exhibited less loss of microvessel proteins following tMCAO. Notably, primary endothelial cell cultures were rescued from oxygen-glucose deprivation (OGD) by lentiviral HSP27 overexpression according to four viability assays, supporting a direct effect on this cell type. Finally, HSP27 overexpression reduced the appearance of neutrophils in the brain and inhibited the secretion of five cytokines. These findings reveal a novel role for HSP27 in attenuating ischemia/reperfusion injury - the maintenance of BBB integrity. Endogenous upregulation of HSP27 after ischemia in wild-type animals may exert similar protective functions and warrants further investigation. Exogenous enhancement of HSP27 by rational drug design may lead to future therapies against a host of injuries, including but not limited to a harmful breach in brain vasculature.
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影响因子：
6.3
作者：
Doeppner, Thorsten R.;Nagel, Florian;Baehr, Mathias
通讯作者：
Baehr, Mathias
影响因子：
4.4
作者：
Bechtold, DA;Brown, IR
通讯作者：
Brown, IR
影响因子：
4.8
作者：
Havasi, Andrea;Li, Zhijian;Borkan, Steven C.
通讯作者：
Borkan, Steven C.
影响因子：
37.8
作者：
Hollander, JM;Martin, JL;Dillmann, WH
通讯作者：
Dillmann, WH
DOI：
10.1097/01.wcb.0000122745.72175.d5
发表时间：
2004-07-01
影响因子：
6.3
作者：
Ayata, C;Dunn, AK;Moskowitz, MA
通讯作者：
Moskowitz, MA