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.
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Authors | Takahisa Noto, Yasuhisa Furuichi, Masayuki Ishiye, Nobuya Matsuoka, Ichiro Aramori, Seitaro Mutoh, Takehiko Yanagihara |
Journal | Biological & pharmaceutical bulletin
(Biol Pharm Bull)
Vol. 30
Issue 2
Pg. 313-7
(Feb 2007)
ISSN: 0918-6158 [Print] Japan |
PMID | 17268072
(Publication Type: Journal Article)
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Chemical References |
- MAP2 protein, rat
- Microtubule-Associated Proteins
- Neuroprotective Agents
- Nitroimidazoles
- Intercellular Adhesion Molecule-1
- pimonidazole
- Tacrolimus
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Topics |
- Animals
- Blood Platelets
(drug effects, physiology)
- Brain Ischemia
(drug therapy, metabolism, pathology)
- Cell Adhesion
(drug effects)
- Cerebral Cortex
(drug effects, metabolism, pathology)
- Granulocytes
(drug effects, physiology)
- Infarction, Middle Cerebral Artery
(drug therapy, metabolism, pathology)
- Intercellular Adhesion Molecule-1
(metabolism)
- Male
- Microtubule-Associated Proteins
(metabolism)
- Neuroprotective Agents
(pharmacology)
- Nitroimidazoles
(metabolism)
- Rats
- Rats, Wistar
- Tacrolimus
(pharmacology)
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