Combination of Bardoxolone and DMF Ameliorates Cerebral Ischemia/Reperfusion Injury in Male Rats

Abstract

Background: Ischemic stroke has been ranked as the second cause of death in patients worldwide. Inflammation which is activated during cerebral Ischemia/ Reperfusion (I/R) is an important mechanism leading to brain injury. The present study aimed to investigate the effect of Berberine on cerebral I/R injury and the role of inflammation in this process.
Material and Methods: The study was carried out on 36 Wistar-albino rats, divided into four groups including Sham group, I/R group, I/R+ (control-vehicle DMSO) and I/R+ Berberine 5 mg/kg injected intraperitoneally 1 hour before induction of ischemia. Measurement of brain tissue IL-1β, ICAM-1 (Intercellular Adhesion Molecule-1), caspase-3, Notch 1 and Jagged 1 was done after one hour of reperfusion in addition to the assessment of the brain infracted area and histopathological analysis.
Results: Berberine attenuates cerebral I/R injury induced increase in inflammatory cytokine (IL-1β), adhesion molecule (ICAM-1) and proapoptotic enzyme (caspase-3). Additionally, it reduces the size of infarcted area and histopathological damage; such protective effect could be mediated by Notch 1 signaling pathway since Berberine further unregulated the increased levels of Notch 1 and Jagged 1 seen in the brain with I/R injury.
Conclusions: Berberine has a neurocytoprotective outcome against cerebral I/R injury which is manifested as anti-inflammatory anti-apoptotic effect that preserved cell structure and viability, in the meantime this effect could be mediated by Notch 1 signaling pathway.