title: Neuroprotective effect of masitinib in rats with postischemic stroke.
abstract: This study evaluated the therapeutic potential of masitinib, an oral tyrosine kinase inhibitor with activity against c-Kit and platelet-derived growth factor receptors (PDGFR), to reduce ischemic brain area and neurological deficit. Using a well-established filament model of ischemic stroke in rats, the responses to oral treatment with masitinib alone or in combination with recombinant tissue plasminogen activator (rt-PA) were compared to those after rt-PA (10 mg/kg intravenously (i.v.)) monotherapy. In both cases, two doses of masitinib were used--25 or 100 mg/kg, twice per day. Ischemic brain area and the neurological deficit were assessed using the triphenyltetrazolium chloride (TTC) method and behavioral neurological tests, respectively. Masitinib, as a single agent, reduced significantly the infarct size, as compared with the stroke control group. Brain ischemic area decreased from 9.14 to 4.36 % (25 mg/kg) or 2.60 % (100 mg/kg). Moreover, a combined treatment of masitinib with rt-PA produced a stronger effect than the one observed after each of the compound alone. The size of the brain ischemic area (rt-PA 1.67 %) was further reduced to 0.83 or 0.7 % at masitinib doses of 25 and 100 mg/kg, respectively. Masitinib reduced significantly brain ischemia induced by experimental stroke and potentiated the therapeutic effect of rt-PA.
authors.affiliation: Department of Pharmacology, Medical University of Gdansk, Debowa 23, 80-204, Gdansk, Poland, ikocic@gumed.edu.pl.
authors.forename: Ivan
authors.initials: I
authors.lastname: Kocic
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Kowianski
authors.forename: Izabela
authors.initials: I
authors.lastname: Rusiecka
authors.forename: Grazyna
authors.initials: G
authors.lastname: Lietzau
authors.forename: Colin
authors.initials: C
authors.lastname: Mansfield
authors.forename: Alain
authors.initials: A
authors.lastname: Moussy
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Patrice
authors.initials: P
authors.lastname: Dubreuil
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010880:Piperidines; D011725:Pyridines; D017208:Rats, Wistar; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D013844:Thiazoles / Q000627:therapeutic use*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D006993:Hypnotics and Sedatives; D018696:Neuroprotective Agents; D010880:Piperidines; D011725:Pyridines; D013844:Thiazoles; D010959:Tissue Plasminogen Activator; C526575:masitinib