title: Treatment of stroke with liposomal neuroprotective agents under cerebral ischemia conditions.
abstract: Since the proportion of patients given thrombolytic therapy with tissue plasminogen activator (t-PA) is very limited because of the narrow therapeutic window, the development of new therapies for ischemic stroke has been desired. We previously reported that liposomes injected intravenously accumulate in the ischemic region of the brain via disruption of the blood-brain barrier that occurs under cerebral ischemia. In the present study, we investigated the efficacy of a liposomal neuroprotective agent in middle cerebral artery occlusion (MCAO) rats to develop ischemic stroke therapy prior to the recovery of cerebral blood flow. For this purpose, PEGylated liposomes encapsulating FK506 (FK506-liposomes) were prepared and injected intravenously into MCAO rats after a 1-h occlusion. This treatment significantly suppressed the expansion of oxidative stress and brain cell damage. In addition, administration of FK506-liposomes before reperfusion significantly ameliorated motor function deficits of the rats caused by ischemia/reperfusion injury. These findings suggest that FK506-liposomes effectively exerted a neuroprotective effect during ischemic conditions, and that combination therapy with a liposomal neuroprotectant plus t-PA could be a promising therapeutic strategy for ischemic stroke.
authors.affiliation: Department of Medical Biochemistry, University of Shizuoka Graduate School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan; Japan Society for the Promotion of Science (JSPS), 8 Ichiban-cho, Chiyoda-ku, Tokyo 102-8472, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fukuta
authors.affiliation: Department of Medical Biochemistry, University of Shizuoka Graduate School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Department of Medical Biochemistry, University of Shizuoka Graduate School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Asai
authors.affiliation: Department of Medical Biochemistry, University of Shizuoka Graduate School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sato
authors.affiliation: Department of Medical Biochemistry, University of Shizuoka Graduate School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Department of Medical Biochemistry, University of Shizuoka Graduate School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.affiliation: Department of Medical Biochemistry, University of Shizuoka Graduate School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: oku@u-shizuoka-ken.ac.jp.
authors.forename: Naoto
authors.initials: N
authors.lastname: Oku
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control*; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008081:Liposomes; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy; D020521:Stroke / Q000517:prevention & control*; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D008081:Liposomes; D018696:Neuroprotective Agents; D011092:Polyethylene Glycols; D016559:Tacrolimus
keywords: FK506; Ischemic stroke; Liposomes; Middle cerebral artery occlusion; Neuroprotectants; Thrombolytic therapy