title: Serum S-100b protein as a biomarker for the assessment of neuroprotectants.
abstract: The study of biomarkers associated with stroke has proved to be of considerable utility. The astroglial protein S-100b is a candidate marker for cerebral tissue damage. We used a rat embolic model produced by injection of microspheres to demonstrate that serum S-100b is a useful biochemical marker for ischemic brain injury. Serum S-100b levels were significantly increased following microsphere injection, which was closely correlated with the development of brain edema. We found that structurally and mechanistically independent neuroprotective agents, such as 3-[2-[4-(3-chloro-2-methylphenylmethyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate (DY-9760e), a novel calmodulin antagonist, and the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801, are capable of attenuating increased serum S-100b levels and brain edema. In contrast, the hyperosmolar agent glycerol, which has no direct neuroprotective action, had little effect on serum S-100b levels, despite a significant decrease in brain water content. These results suggest that lowering of serum S-100b is mediated by neuroprotection against ischemic brain injury. Thus, serum S-100b reflects the extent of brain damage following cerebral ischemia and serves as a useful biomarker for the assessment of neuroprotectants.
authors.affiliation: New Product Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., 1-16-13 Kitakasai 1-Chome, Edogawa-ku, Tokyo 134-8630, Japan. shiram8s@daiichipharm.co.jp
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Shirasaki
authors.forename: Naoko
authors.initials: N
authors.lastname: Edo
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sato
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology; D002545:Brain Ischemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D020766:Intracranial Embolism / Q000150:complications; D008297:Male; D008863:Microspheres; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood* / Q000187:drug effects
chemical_list: D015415:Biomarkers; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins