SerpinA3N attenuates ischemic stroke injury by reducing apoptosis and neuroinflammation.

Abstract

ObjectiveTo assess the effect of serine protein inhibitor A3N (serpinA3N) in ischemic stroke and to explore its mechanism of action.MethodsMouse ischemic stroke model was induced by transient middle cerebral artery occlusion followed by reperfusion. The expression pattern of serpinA3N was assessed using immunofluorescence, Western blot analysis, and real‐time quantitative PCR. An adeno‐associated virus (AAV) and recombinant serpinA3N were administered. Additionally, co‐immunoprecipitation‐mass spectrometry and immunofluorescence co‐staining were used to identify protein interactions.ResultsSerpinA3N was upregulated in astrocytes and neurons within the ischemic penumbra after stroke in the acute phase. The expression of serpinA3N gradually increased 6 h after reperfusion, peaked on the day 2–3, and then decreased by day 7. Overexpression of serpinA3N by AAV significantly reduced the infarct size and improved motor function, associated with alleviated inflammation and oxidative stress. SerpinA3N treatment also reduced apoptosis both in vivo and in vitro. Co‐immunoprecipitation‐mass spectrometry and Western blotting revealed that clusterin interacts with serpinA3N, and Akt‐mTOR pathway members were upregulated by serpinA3N both in vivo and in vitro.ConclusionsSerpinA3N is expressed in astrocytes and penumbra neurons after stroke in mice. It reduces brain damage possibly via interacting with clusterin and inhibiting neuronal apoptosis and neuroinflammation.