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

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 Hsp7...

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Published in:	Drug design, development and therapy Vol. 8; no. default; pp. 639 - 650
Main Authors:	Shevtsov, Maxim A, Nikolaev, Boris P, Yakovleva, Ludmila Y, Dobrodumov, Anatolii V, Dayneko, Anastasiy S, Shmonin, Alexey A, Vlasov, Timur D, Melnikova, Elena V, Vilisov, Alexander D, Guzhova, Irina V, Ischenko, Alexander M, Mikhrina, Anastasiya L, Galibin, Oleg V, Yakovenko, Igor V, Margulis, Boris A
Format:	Journal Article
Language:	English
Published:	New Zealand Dove Medical Press Limited 01-01-2014 Taylor & Francis Ltd Dove Press Dove Medical Press
Subjects:	Administration, Intravenous alginate granules Alginates Alginic acid Animals Annexin V Apoptosis Brain Brain Ischemia - drug therapy Brain research Care and treatment Cerebral blood flow Cerebral infarction Cerebral ischemia Chemical compounds Cytokines Disease Models, Animal focal ischemia Heat shock proteins HSP70 Heat-Shock Proteins - administration & dosage HSP70 Heat-Shock Proteins - therapeutic use Hsp70 protein Hyperthermia Infarction Ischemia Laboratory animals Magnetic resonance imaging Male Neuroprotection neurotherapy NMR Nuclear magnetic resonance Occlusion Original Research Pharmaceutical research Pharmacology Rats Rats, Wistar Recombinant Proteins - administration & dosage Recombinant Proteins - therapeutic use Reperfusion Rodents Stroke Triphenyltetrazolium chloride Russia alginate granules focal ischemia neurotherapy stroke neuroprotection
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	1177-8881 1177-8881
DOI:	10.2147/dddt.s62024