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 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 blood brain barrier (BBB) and accumulate in the ischemic penumbra. At 3 d after I/R injury, NPcurcumin inhibited the increase in MMP9, attenuated the decrease in occludin and ZO-1, and maintained BBB integrity. NPcurcumin effectively reduce the number of activated M1-microglia, and weaken the increase of TNF-α and IL-1β. Furtherly, NPcurcumin also reduced infarcted size and improved function recovery.