Neuroprotective and neurotoxic effects of cyclosporine A on transient focal ischemia in mdr1a knockout mice.
The proper dose of cyclosporine A as a neuroprotective agent was investigated using the middle cerebral artery occlusion model of mdr1a knockout mice. After a 30-min occlusion period, reperfusion was performed and the vehicle or cyclosporine A (1 mg/kg or 10 mg/kg x 2) was intraperitoneally administered to each animal model group. Forty eight hours after reperfusion, infarction volume in the 1 mg/kg cyclosporine A group was significantly less than that seen in the vehicle group, although, in the high dose cyclosporine A group, infarction volumes were significantly higher than those seen in the vehicle group. These results demonstrate that cyclosporine A shows not only anti-ischemic effects, but also neurotoxic effects depending on the dosage penetrating into the brain.
Murozono
Michihiro
M
Department of Anesthesiology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. pagupagupagu@hotmail.com
Matsumoto
Shohei
S
Matsumoto
Eriko
E
Isshiki
Atsushi
A
Watanabe
Yasuo
Y
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics* / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D002546:Ischemic Attack, Transient / Q000150:complications / Q000517:prevention & control*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D018696:Neuroprotective Agents; D016572:Cyclosporine; C095122:multidrug resistance protein 3