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Exogenous recombinant Hsp70 mediates neuroprotection after photothrombotic stroke.
Cell Stress and Chaperones ( IF 3.8 ) Pub Date : 2020-09-01 , DOI: 10.1007/s12192-020-01159-0
S Demyanenko 1 , V Nikul 1 , S Rodkin 1 , A Davletshin 2 , M B Evgen'ev 2 , D G Garbuz 2
Affiliation  

Ischaemic stroke is an acute interruption of the blood supply to the brain, which leads to rapid irreversible damage to nerve tissue. Ischaemic stroke is accompanied by the development of neuroinflammation and neurodegeneration observed around the affected brain area. Heat shock protein 70 (Hsp70) facilitates cell survival under a variety of different stress conditions. Hsp70 may be secreted from cells and exhibits cytoprotective activity. This activity most likely occurs by decreasing the levels of several proinflammatory cytokines through interaction with a few receptors specific to the innate immune system. Herein, we demonstrated that intranasal administration of recombinant human Hsp70 shows a significant twofold decrease in the volume of local ischaemia induced by photothrombosis in the mouse prefrontal brain cortex. Our results revealed that intranasal injections of recombinant Hsp70 decreased the apoptosis level in the ischaemic penumbra, stimulated axonogenesis and increased the number of neurons producing synaptophysin. Similarly, in the isolated crayfish stretch receptor, consisting of a single sensory neuron surrounded by the glial envelope, exogenous Hsp70 significantly decreased photoinduced apoptosis and necrosis of glial cells. The obtained data enable one to consider human recombinant Hsp70 as a promising compound that could be translated from the bench into clinical therapies.



中文翻译:

外源性重组 Hsp70 介导光血栓形成中风后的神经保护作用。

缺血性中风是大脑血液供应的急性中断,导致神经组织快速不可逆转的损伤。缺血性中风伴随着在受影响的大脑区域周围观察到的神经炎症和神经变性的发展。热休克蛋白 70 (Hsp70) 在各种不同的压力条件下促进细胞存活。Hsp70 可以从细胞中分泌出来并表现出细胞保护活性。这种活性很可能是通过与一些对先天免疫系统具有特异性的受体相互作用来降低几种促炎细胞因子的水平而发生的。在此,我们证明了重组人 Hsp70 的鼻内给药显示小鼠前额叶脑皮层中光血栓形成引起的局部缺血体积显着减少了两倍。我们的研究结果表明,鼻内注射重组 Hsp70 可降低缺血半暗带的细胞凋亡水平,刺激轴突生成并增加产生突触素的神经元数量。同样,在分离的小龙虾拉伸受体中,由被神经胶质包膜包围的单个感觉神经元组成,外源性 Hsp70 显着降低了光诱导的神经胶质细胞凋亡和坏死。获得的数据使人们能够将人类重组 Hsp70 视为一种有前途的化合物,可以从实验室转化为临床治疗。由被神经胶质包膜包围的单个感觉神经元组成,外源性 Hsp70 显着降低了光诱导的神经胶质细胞凋亡和坏死。获得的数据使人们能够将人类重组 Hsp70 视为一种有前途的化合物,可以从实验室转化为临床治疗。由被神经胶质包膜包围的单个感觉神经元组成,外源性 Hsp70 显着降低了光诱导的神经胶质细胞凋亡和坏死。获得的数据使人们能够将人类重组 Hsp70 视为一种有前途的化合物,可以从实验室转化为临床治疗。

更新日期:2020-09-01
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