title: Tacrolimus (FK506) limits accumulation of granulocytes and platelets and protects against brain damage after transient focal cerebral ischemia in rat.
abstract: We investigated the neuroprotective effect of tacrolimus (FK506) on the ischemia-reperfusion injury caused by transient focal brain ischemia induced by middle cerebral artery (MCA) occlusion for 60 min in rats. Neuronal damage visualized as a decrease of MAP2 immunoreactivity was observed in the cerebral cortex at 9 h after MCA occlusion and further expanded at 24 h. Hypoxic areas visualized with an immunohistochemical reaction for 2-nitroimidazole, a hypoxia marker (hypoxyprobe-1), and accumulation of granulocytes and platelets were also observed at 9 h and 24 h after MCA occlusion. Tacrolimus (1 mg/kg, i.v.), administered immediately after MCA occlusion, attenuated cortical damage and decreased the hypoxyprobe-1 positive area, as well as the number of granulocytes and platelets at 24 h after MCA occlusion. Immunohistochemical analysis showed that tacrolimus reduced the number of blood vessels positively stained for ICAM-1, E-selectin and P-selection. These results suggested that tacrolimus limited attachment of granulocytes and platelets to blood vessels by inhibiting the expression of adhesion molecules and protected neuronal tissue from hypoxic insults.
authors.affiliation: Medicinal Biology Research Laboratories, Astellas Pharmaceutical Inc., Osaka, Japan. takahisa.noto@jp.astellas.com
authors.forename: Takahisa
authors.initials: T
authors.lastname: Noto
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Furuichi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ishiye
authors.forename: Nobuya
authors.initials: N
authors.lastname: Matsuoka
authors.forename: Ichiro
authors.initials: I
authors.lastname: Aramori
authors.forename: Seitaro
authors.initials: S
authors.lastname: Mutoh
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yanagihara
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000494:pharmacology*
chemical_list: C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D009593:Nitroimidazoles; D018799:Intercellular Adhesion Molecule-1; C033815:pimonidazole; D016559:Tacrolimus