Neuroprotective effects of protein tyrosine phosphatase 1B inhibitor on cerebral ischemia/reperfusion in mice.

In this study, we confirmed the ameliorative effects of KY-226 on ischemia/reperfusion (I/R) injury using a murine model of middle cerebral artery occlusion (MCAO). ICR mice were subjected to MCAO for 2 h followed by reperfusion. Although KY-226 permeability was poor through the blood-brain barrier (BBB) of normal mice, it could penetrate through the BBB of mice after I/R insult. Intraperitoneal KY-226 administration elicited dose-dependent reductions in infarcted brain areas and improved neurological deficits. The neuroprotective effects of KY-266 were obtained when administered within 0.5 h after reperfusion. KY-226 (10 mg/kg) also restored reduced Akt phosphorylation and eNOS phosphorylation (Ser-1177) levels following I/R insult. Moreover, 10 mg/kg of KY-226 improved I/R-induced decreased extracellular signal-regulated kinase (ERK) phosphorylation. Furthermore, KY-226 attenuated the generation of reactive oxygen species (ROS) in mouse cortex. These results suggest that KY-226 may act as a novel therapeutic candidate for ischemic stroke. Activation of Akt and ERK possibly underlie the neuroprotective mechanism of KY-226. PMID: 29705606 [PubMed - as supplied by publisher]
Source: Brain Research - Category: Neurology Authors: Tags: Brain Res Source Type: research