title: Serum S100B indicates successful combination treatment with recombinant tissue plasminogen activator and MK-801 in a rat model of embolic stroke.
abstract: In recent years, serum S100B has been used as a secondary endpoint in some clinical trials in which serum S100B has successfully indicated the benefits or harm done by tested agents. However, few reports describe serum S100B as an indicator of the efficiency of neuroprotective treatment in experimental stroke models, although serum S100B may be as useful for histological and functional evaluations of neuroprotective treatments as in clinical trials. The present study seeks to investigate the possibility that serum S100B reflects successful combined treatment with rt-PA and MK-801 in an embolic stroke rat model. An embolic stroke model of rats was produced via intra-arterial autologous clot injection, after which serum S100B levels were measured 24 h after embolism and the association of serum S100B levels with brain edema volume and infarct volume investigated. Combination treatment with rt-PA and MK-801 significantly attenuated the elevation of serum S100B, which correlated significantly with reductions in brain edema resulting from combination treatment. These findings suggest that serum S100B is a simple and objective indicator for successful neuroprotective therapy and would help seeking partners for combination treatments with rt-PA in an embolic stroke rat model. Assessments of the efficacy of combination treatments with rt-PA and neuroprotectants using serum S100B would facilitate translational research bridging laboratory and bedsides because serum S100B functions as a common marker in both rats and human patients suffering from ischemic stroke.
authors.affiliation: Medical Research Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama 331-9530, Japan. yu.tanaka@po.rd.taisho.co.jp
authors.forename: Yu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Marumo
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Omura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D009414:Nerve Growth Factors / Q000097:blood*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood*; D020521:Stroke / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D013923:Thromboembolism; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C579158:S100b protein, rat; D016291:Dizocilpine Maleate; D010959:Tissue Plasminogen Activator