title: The effect of treatment with a sustained-release prostacyclin analogue (ONO-1301-loaded PLGA microsphere) on short-term memory impairment in rats with transient global cerebral ischemia.
abstract: The purpose of this study was to prepare the ONO-1301 loaded poly(lactide-co-glycolide) microsphere (ONO-1301 PLGA MS) and to evaluate neuroprotective effects for short-term memory by a single subcutaneous injection of ONO-1301 PLGA MS on repeated induction of cerebral ischemia (2 × 10-min with a 1-min interval) in rat. Drug release profiles from ONO-1301 PLGA MS in vitro and in vivo were evaluated. The extent of ischemic injury was assessed behaviourally using the passive avoidance test and histopathologically by evaluating hippocampal CA1 pyramidal damage on day 42 after ischemia. Experiments in vitro showed that the release of ONO-1301 from ONO-1301 PLGA MS was sustained for approximately 3 weeks with maintenance of steady plasma levels. The neuroprotective effect was shown by treatment with ONO-1301 PLGA MS from 2 days after induction of ischemia behaviourally and histopathologically. These results suggest that ONO-1301 PLGA MS can limit short-term learning injury following global cerebral ischemia.
authors.affiliation: Faculty of Pharmaceutical Sciences, Department of Clinical Pharmaceutics, Mukogawa Women's University, Hyogo, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Hazekawa
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sakai
authors.forename: Miyako
authors.initials: M
authors.lastname: Yoshida
authors.forename: Tamami
authors.initials: T
authors.lastname: Haraguchi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Uchida
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004195:Disease Models, Animal; D004339:Drug Compounding; D011464:Epoprostenol / Q000031:analogs & derivatives*; D006624:Hippocampus / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy*; D008570:Memory, Short-Term / Q000187:drug effects; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011725:Pyridines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D011725:Pyridines; C105488:ONO 1301; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011464:Epoprostenol