Targeting Smox Is Neuroprotective and Ameliorates Brain Inflammation in Cerebral Ischemia/Reperfusion Rats

: Spermine oxidase (Smox) is a member of the polyamine oxidases and has been demonstrated to be involved in ischemic brain damage. In this study, we found that Smox expression was increased in a rat middle cerebral artery occlusion (MCAO) model and in cultured primary neurons after oxygen-glucose deprivation and reoxygenation (OGD/R). Smox downregulation by the adeno-associated virus RNA interference system significantly reduced the MCAO-induced brain infarct volume and neurological deficits and decreased neuronal apoptosis and inflammatory reactions. In addition, significant microglial activation and increased IL-6 and TNF-α expression were observed in microglia treated with supernatant from neurons after OGD/R. However, a significant reduction in microglial activation as well as IL-6 and TNF-α expression was observed in microglia treated with supernatant from Smox downregulated neurons after OGD/R. Therefore, the results indicated that Smox is an important mediator of cerebral ischemia injury and may be a therapeutic target for cerebral ischemia patients.