Exogenous recombinant Hsp70 mediates neuroprotection after photothrombotic stroke
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ORIGINAL PAPER
Exogenous recombinant Hsp70 mediates neuroprotection after photothrombotic stroke S. Demyanenko 1 & V. Nikul 1 & S. Rodkin 1 & A. Davletshin 2 & M. B. Evgen’ev 2
&
D. G. Garbuz 2
Received: 20 June 2020 / Revised: 21 August 2020 / Accepted: 25 August 2020 # Cell Stress Society International 2020
Abstract 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. Keywords Photothrombotic stroke . Hsp70 . Neuroprotection . GAP43 . Synaptophysin
Abbreviations PTS Photothrombotic stroke Hsp70 Heat shock protein 70 SYP Synaptophysin
Introduction Stroke is the second leading cause of human disability and death worldwide (James et al. 2020; Powers et al. 2018). Ischaemic stroke (approximately 80% of all strokes) occurs due to a sudden rapid drop in cerebral blood flow that lasts for minutes, reduces the oxygen and glucose supply of a tissue, * M. B. Evgen’ev [email protected] 1
Laboratory “Molecular Neurobiology”, Academy of Biology and Biotechnology, Southern Federal University, Prospect Stachki 194/1, Rostov-on-Don 344090, Russia
2
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str. 32, Moscow 119991, Russia
and leads to a decrease in ATP production and necrosis. The toxic factors (glutamate, K+-mediated depolarization, reactive oxygen species (ROS), oedema, etc.) spread slowly, over the course of several hours, from the infarction core to the surrounding tissue and expand the injured area. It is assumed that cells in the transition zone (penumbra) may be saved during the next 2–6 h (“therapeutic window”), or even during the first 24 h after stroke (Moskowitz et al. 2010; Khoshnam et al. 2017). There are two main approaches fo
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