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Tytuł pozycji:

Neurotherapeutic activity of the recombinant heat shock protein Hsp70 in a model of focal cerebral ischemia in rats

Tytuł :
Neurotherapeutic activity of the recombinant heat shock protein Hsp70 in a model of focal cerebral ischemia in rats
Autorzy :
Shevtsov MA
Nikolaev BP
Yakovleva LY
Dobrodumov AV
Dayneko AS
Shmonin AA
Vlasov TD
Melnikova EV
Vilisov AD
Guzhova IV
Ischenko AM
Mikhrina AL
Galibin OV
Yakovenko IV
Margulis BA
Pokaż więcej
Temat :
Therapeutics. Pharmacology
RM1-950
Źródło :
Drug Design, Development and Therapy, Vol 2014, Iss default, Pp 639-650 (2014)
Wydawca :
Dove Medical Press, 2014.
Rok publikacji :
2014
Kolekcja :
LCC:Therapeutics. Pharmacology
Typ dokumentu :
article
Opis pliku :
electronic resource
Język :
English
ISSN :
1177-8881
Relacje :
http://www.dovepress.com/neurotherapeutic-activity-of-the-recombinant-heat-shock-protein-hsp70--peer-reviewed-article-DDDT; https://doaj.org/toc/1177-8881
Dostęp URL :
https://doaj.org/article/637b11c7100a40e4a179f17e97998803
Numer akcesji :
edsdoj.637b11c7100a40e4a179f17e97998803
Czasopismo naukowe
Maxim A Shevtsov,1,2 Boris P Nikolaev,3 Ludmila Y Yakovleva,3 Anatolii V Dobrodumov,4 Anastasiy S Dayneko,5 Alexey A Shmonin,5,6 Timur D Vlasov,5 Elena V Melnikova,5 Alexander D Vilisov,4,5 Irina V Guzhova,1 Alexander M Ischenko,3 Anastasiya L Mikhrina,7 Oleg V Galibin,5 Igor V Yakovenko,2 Boris A Margulis1 1Institute of Cytology of the Russian Academy of Sciences (RAS), St Petersburg, Russia; 2AL Polenov Russian Research Scientific Institute of Neurosurgery, St Petersburg, Russia; 3Research Institute of Highly Pure Biopreparations, St Petersburg, Russia; 4Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS), St Petersburg, Russia; 5First St Petersburg IP Pavlov State Medical University, St Petersburg, Russia; 6Federal Almazov Medical Research Centre, St Petersburg, Russia; 7IM Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (RAS), St Petersburg, Russia Abstract: Recombinant 70 kDa heat shock protein (Hsp70) is an antiapoptotic protein that has a cell protective activity in stress stimuli and thus could be a useful therapeutic agent in the management of patients with acute ischemic stroke. The neuroprotective and neurotherapeutic activity of recombinant Hsp70 was explored in a model of experimental stroke in rats. Ischemia was produced by the occlusion of the middle cerebral artery for 45 minutes. To assess its neuroprotective capacity, Hsp70, at various concentrations, was intravenously injected 20 minutes prior to ischemia. Forty-eight hours after ischemia, rats were sacrificed and brain tissue sections were stained with 2% triphenyl tetrazolium chloride. Preliminary treatment with Hsp70 significantly reduced the ischemic zone (optimal response at 2.5 mg/kg). To assess Hsp70’s neurotherapeutic activity, we intravenously administered Hsp70 via the tail vein 2 hours after reperfusion (2 hours and 45 minutes after ischemia). Rats were then kept alive for 72 hours. The ischemic region was analyzed using a high-field 11 T MRI scanner. Administration of the Hsp70 decreased the infarction zone in a dose-dependent manner with an optimal (threefold) therapeutic response at 5 mg/kg. Long-term treatment of the ischemic rats with Hsp70 formulated in alginate granules with retarded release of protein further reduced the infarct volume in the brain as well as apoptotic area (annexin V staining). Due to its high neurotherapeutic potential, prolonged delivery of Hsp70 could be useful in the management of acute ischemic stroke. Keywords: focal ischemia, stroke, neuroprotection, neurotherapy, alginate granules

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