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Quinolinyl Nitrone RP19 Induces Neuroprotection after Transient Brain Ischemia
- Source :
- ACS chemical neuroscience. 8(10)
- Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Physiology
Cognitive Neuroscience
Ischemia
Pharmacology
medicine.disease_cause
Biochemistry
Neuroprotection
Brain Ischemia
Brain ischemia
Lipid peroxidation
Rats, Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Occlusion
medicine
Animals
Viability assay
chemistry.chemical_classification
Neurons
Reactive oxygen species
Cell Death
Brain
Infarction, Middle Cerebral Artery
Cell Biology
General Medicine
medicine.disease
Stroke
Disease Models, Animal
030104 developmental biology
Neuroprotective Agents
chemistry
Anesthesia
Quinolines
Nitrogen Oxides
030217 neurology & neurosurgery
Oxidative stress
Subjects
Details
- ISSN :
- 19487193
- Volume :
- 8
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- ACS chemical neuroscience
- Accession number :
- edsair.doi.dedup.....d5545cc9ce6e65eda09d25328c69fd47