title: Neurotherapeutic activity of the recombinant heat shock protein Hsp70 in a model of focal cerebral ischemia in rats.
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.
authors.affiliation: Institute of Cytology of the Russian Academy of Sciences (RAS), St Petersburg, Russia ; AL Polenov Russian Research Scientific Institute of Neurosurgery, St Petersburg, Russia.
authors.forename: Maxim A
authors.initials: MA
authors.lastname: Shevtsov
authors.affiliation: Research Institute of Highly Pure Biopreparations, St Petersburg, Russia.
authors.forename: Boris P
authors.initials: BP
authors.lastname: Nikolaev
authors.affiliation: Research Institute of Highly Pure Biopreparations, St Petersburg, Russia.
authors.forename: Ludmila Y
authors.initials: LY
authors.lastname: Yakovleva
authors.affiliation: Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS), St Petersburg, Russia.
authors.forename: Anatolii V
authors.initials: AV
authors.lastname: Dobrodumov
authors.affiliation: First St Petersburg IP Pavlov State Medical University, St Petersburg, Russia.
authors.forename: Anastasiy S
authors.initials: AS
authors.lastname: Dayneko
authors.affiliation: First St Petersburg IP Pavlov State Medical University, St Petersburg, Russia ; Federal Almazov Medical Research Centre, St Petersburg, Russia.
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Shmonin
authors.affiliation: First St Petersburg IP Pavlov State Medical University, St Petersburg, Russia.
authors.forename: Timur D
authors.initials: TD
authors.lastname: Vlasov
authors.affiliation: First St Petersburg IP Pavlov State Medical University, St Petersburg, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Melnikova
authors.affiliation: Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS), St Petersburg, Russia ; First St Petersburg IP Pavlov State Medical University, St Petersburg, Russia.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Vilisov
authors.affiliation: Institute of Cytology of the Russian Academy of Sciences (RAS), St Petersburg, Russia.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Guzhova
authors.affiliation: Research Institute of Highly Pure Biopreparations, St Petersburg, Russia.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Ischenko
authors.affiliation: IM Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (RAS), St Petersburg, Russia.
authors.forename: Anastasiya L
authors.initials: AL
authors.lastname: Mikhrina
authors.affiliation: First St Petersburg IP Pavlov State Medical University, St Petersburg, Russia.
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Galibin
authors.affiliation: AL Polenov Russian Research Scientific Institute of Neurosurgery, St Petersburg, Russia.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Yakovenko
authors.affiliation: Institute of Cytology of the Russian Academy of Sciences (RAS), St Petersburg, Russia.
authors.forename: Boris A
authors.initials: BA
authors.lastname: Margulis
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D018840:HSP70 Heat-Shock Proteins; D011994:Recombinant Proteins
keywords: alginate granules; focal ischemia; neuroprotection; neurotherapy; stroke