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.

A sustained-release drug-delivery system of synthetic prostacyclin agonist, ONO-1301SR: a new reagent to enhance cardiac tissue salvage and/or regeneration in the damaged heart

“…Hazekawa et al [93] reported in 2012 that a single subcutaneous injection of ONO-1301SR into the rats that were subjected to repeated induction of cerebral ischaemia yielded a short-term functional and histopathological recovery. The same groups reported in 2012 that repeated ONO-1301SR administration reduced ischaemic damage of rats that were subjected to middle cerebral artery occlusion [94].…”