Nano-Curcumin Simultaneously Protects the Blood–Brain Barrier and Reduces M1 Microglial Activation During Cerebral Ischemia–Reperfusion Injury

Oxidative stress and inflammation are two important pathophysiological mechanisms that arouse neuronal apoptosis and cerebral damage after ischemia/reperfusion (I/R) injury. Here, we hypothesized that curcumin-encapsulated nanoparticles (NPcurcumin) could reduce oxidative stress and inflammation in the ischemic penumbra via protecting the blood-brain barrier (BBB) and inhibiting M1-microglial activation. Under oxidative stress conditions in vitro, we found that NPcurcumin protected microvascular endothelial cells against oxidative stress and reduced BBB permeability. In vivo, NPcurcumin could cross the BBB and accumulate in the ischemic penumbra. At 3 d after I/R injury, NPcurcumin inhibited the increase in MMP-9, attenuated the decrease in occludin and zona occluden-1, and maintained BBB integrity. NPcurcumin effectively reduced the number of activated M1 microglia and weakened the increase in TNF-α and IL-1β. Furthermore, NPcurcumin also reduced the infarct size and improved function recovery.