The protective effects of curcumin in cerebral ischemia and reperfusion injury through PKC-θ signaling
Yun Mo, Erli Yue, Nan Shi, Kangyong Liu
Abstract
Ischemic stroke is a common cerebrovascular disease with the main cause considered to be cerebral ischemia and reperfusion (I/R), which exerts irreparable injury on nerve cells. Thus, the development of neuroprotective drugs is an urgent concern. Curcumin, a known antioxidant, has been found to have neuroprotective effects. To determine the protective mechanism of curcumin in ischemic stroke, oxygen and glucose deprivation/reoxygenation (OGD/R) was used to treat PC12 cells to mimic the cerebral I/R cell model. Curcumin (20 μM) was applied to OGD/R PC12 cells, followed by Ca2+ concentration, transepithelial electrical resistance (TEER), and cell permeability measurements. The results showed that OGD/R injury induced a decrease in TEER and increases in Ca2+ concentration and cell permeability. In contrast, curcumin alleviated these effects. The protein kinase C θ (PKC-θ) was associated with the protective function of curcumin in the OGD/R cell model. Moreover, the middle cerebral artery occlusion and reperfusion model (MCAO/R) was applied to simulate the I/R rat model. Our results demonstrated that curcumin could reverse the MCAO/R-induced increase in Ca2+ concentration and blood–brain barrier (BBB) disruption. Our study demonstrates the mechanisms by which curcumin exhibited a protective function against cerebral I/R through PKC-θ signaling by reducing BBB dysfunction.