There is a need to develop additional effective
therapies for
ischemic stroke.
Nitrones, which were first developed as
reactive oxygen species (ROS)-trapping compounds, have been proposed as
neuroprotective agents for
ischemic stroke, a ROS-related disorder. The previous reported ROS-trapping compound, quinolyl nitrone RP19, is here being assayed to induce neuroprotection to
ischemia-reperfusion injury in three experimental
ischemia models: (i)
oxygen-
glucose deprivation (OGD) on primary neuronal cultures; (ii) transient global
cerebral ischemia in four-vessel occlusion model; and (iii) transient focal
cerebral ischemia in
middle cerebral artery occlusion (tMCAO) model. RP19 (50 μM) induced long-term neuroprotection at 5 days of recovery after OGD in primary neuronal cultures, evaluated by cell viability assay, and decreased both ROS formation and lipid peroxidation upon recovery after OGD. Furthermore, treatment of animals with RP19 at the onset of reperfusion after either global or focal
ischemia, at the dose range that was demonstrated to be neuroprotective in neuronal cultures, decreased neuronal death and apoptosis induction, reduced the size of
infarct, and improved the neurological deficit scores after 48 h or 5 days of reperfusion after
ischemia. The molecule proposed, quinolyl nitrone RP19, induced substantial neuroprotection on experimental
ischemia in neuronal cells, and against ischemic injury following transient
brain ischemia in treated animals. This molecule may have potential therapeutic interest in
ischemic stroke and to reduce the reoxygenation-induced injury after induced reperfusion.