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Exogenous recombinant Hsp70 mediates neuroprotection after photothrombotic stroke

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Cell Stress and Chaperones Aims and scope

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.

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Abbreviations

PTS:

Photothrombotic stroke

Hsp70:

Heat shock protein 70

SYP:

Synaptophysin

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Funding

Expression and isolation of human recombinant Hsp70 was performed using funding provided by Russian Science Foundation grant #19-14-00167 (D.G). All studies with two models of experimental stroke were funded by the Ministry of Science and Higher Education of Russian Federation grant #0852-2020-0028.

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Authors and Affiliations

  1. Laboratory “Molecular Neurobiology”, Academy of Biology and Biotechnology, Southern Federal University, Prospect Stachki 194/1, Rostov-on-Don, 344090, Russia

    S. Demyanenko, V. Nikul & S. Rodkin

  2. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str. 32, Moscow, 119991, Russia

    A. Davletshin, M. B. Evgen’ev & D. G. Garbuz

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  1. S. Demyanenko
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  2. V. Nikul
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  5. M. B. Evgen’ev
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  6. D. G. Garbuz
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Correspondence to M. B. Evgen’ev.

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Demyanenko, S., Nikul, V., Rodkin, S. et al. Exogenous recombinant Hsp70 mediates neuroprotection after photothrombotic stroke. Cell Stress and Chaperones 26, 103–114 (2021). https://doi.org/10.1007/s12192-020-01159-0

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