Search

Cerebral ischemic stroke leads to mitochondrial alterations which are key factors for initiation of various cascades resulting in neuronal damage. Dopamine D2 receptor (D2R) agonist, Sumanirole (SUM) has been reported to possess anti-inflammatory, anti-oxidant, and anti-apoptotic properties. However, the role of SUM in ischemic stroke (IS) has not been studied yet. The aim of the present study was to investigate the neuroprotective efficiency of SUM against ischemic injury and its possible effect on mitochondrial restorative mechanisms. Transient middle cerebral artery occlusion (tMCAO) was performed in Wistar rats for 90 min occlusion and 22.5 h reperfusion to mimic ischemic stroke. Post- treatment with Sumanirole (0.1 mg/kg and 1 mg/kg; s.c.) was done at 1 h, 6 h, 12 hand 18 h after surgery. In addition, neurobehavioral analysis, mitochondrial reactive oxygen species and mitochondrial membrane potential by flow cytometric analysis, mitochondrial complexes analysis, infarct size evaluation and histological analysis were performed. Sumanirole restored behavioural alterations as measured by rotarod performance, grip strength, adhesive tape removal analysis and neurological deficits. In addition, it also refurbished mitochondrial dysfunction by decreasing mitochondrial reactive oxygen species production, elevating mitochondrial membrane potential and by protecting the activity of mitochondrial complexes along with histological alterations. As a result, infarct sizes were markedly reduced in tMCAO surgery animals. Findings from the study provide evidence that SUM promotes neuronal survival in in vivo model of IS through mitochondria mediated neuroprotective features. • We investigated the neuroprotective efficiency of highly selective dopamine D2 agonist Sumanirole against ischemic injury. • Sumanirole restored behavioural alterations and neurological deficits in a stroke rodent mode. • Mitochondrial dysfunction was attemnuated by decreasing mitochondrial ROS production. • Infarct sizes were markedly reduced in tMCAO surgery animals. • Our study provides evidence for mitochondrial mediated neuroprotective features of Sumanirole against ischemic stroke. [ABSTRACT FROM AUTHOR]