Abstract
Background and PurposeCurcumin, a natural antioxidant isolated from Curcuma longa, has been reported to exert neuroprotective effect in animal models of ischemic stroke. However, the underlying mechanism is still not fully understood. The purpose of this study was to investigate the effect of curcumin treatment on neuronal apoptosis in the periinfarct cortex after cerebral ischemia/reperfusion (I/R) injury and in mouse N2a cells after oxygen‐glucose deprivation/reoxygenation (OGD/R) injury and its underlying mechanism.MethodsThe cerebral I/R injury was established by 1‐hr middle cerebral artery occlusion (MCAO) and reperfusion in mice. Infarct volume was determined by TTC staining, and neurological score was evaluated by mNSS. Cell morphology in the ischemic boundary zone were detected by HE staining. The number and apoptotic rate of neurons in ischemic boundary zone were assayed by immunohistochemistry and TUNEL, respectively. Mouse neuroblastoma N2a cells were subjected to OGD/R. Cell viability was assessed with CCK‐8. The mitochondrial membrane potential was measured using JC‐1 staining. The expression of Bax, Bcl‐2, and caspase‐3 was detected using Western blotting. Besides, cellular distribution of Bax was determined by immunofluorescence assays.ResultsCurcumin treatment reduced infarct volume, improved neurological function, alleviated the morphological damage of neurons, and increased neuronal survival rate after I/R injury in vivo. Moreover, curcumin treatment improved cell viability, reduced cell apoptosis, increased Bcl‐2 protein levels while decreased Bax and caspase‐3 expressions in mouse N2a cells after OGD/R injury. Besides, curcumin treatment inhibited Bax activation and maintained mitochondrial membrane integrity.ConclusionCurcumin promotes neuron survival in vivo and in vitro to exert neuroprotective effects against ischemia injury. Moreover, our results for the first time demonstrated curcumin inhibited ischemia‐induced mitochondrial apoptosis via restricting Bax activation, which may be one of the possible mechanisms underlying the neuroprotective effects of curcumin.
Highlights
Stroke is a leading cause of death and permanent adult disability all over the world and remains a major challenge to public health (Correction to Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association,” 2017)
Apoptosis is one of the major pathways that leads to neuronal death after cerebral ischemia/reperfusion (I/R), and mitochondria are the cellular organelles that play important roles in the apoptotic signaling in ischemic injury (Mattson, Duan, Pedersen, & Culmsee, 2001; Zuo et al, 2014)
As the proapoptotic protein Bax plays a critical role in triggering mitochondrial apoptotic pathway (Kroemer, 2003), we further explored whether curcumin inhibits Bax activation by immunofluorescent assay
Summary
Stroke is a leading cause of death and permanent adult disability all over the world and remains a major challenge to public health (Correction to Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association,” 2017). Cerebral ischemia, is a complex pathophysiologic process, during which excitotoxicity, oxidative stress, inflammation, and dysfunction of ATP production are involved (Benakis, Garcia-Bonilla, Iadecola, & Anrather, 2014; Connolly, Dussmann, Anilkumar, Huber, & Prehn, 2014; Jung et al, 2010; Naito & Yoshikawa, 2006) These pathophysiologic events overlap and intercommunicate, eventually resulting in neuronal death. In dose-response study, mice of CUR group were intraperitoneally injected with curcumin (Sigma-Aldrich, USA) dissolved in normal sterile saline with 1% dimethyl sulfoxide (DMSO) at a dose of 100, 200, 300, 400 mg/kg, immediately after 1 hr of occlusion Both VEH and SHA groups were injected with the same volume of sterile saline with 1% DMSO.
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