Selenoprotein S expression in the rat brain following focal cerebral ischemia

Recent studies on cerebral ischemic stroke have demonstrated the importance of the inflammatory response. Ongoing inflammatory insults have been implicated as a secondary mechanism underlying neuronal injury induced by ischemia, and anti-inflammatory strategies have gained considerable interest. Selenoprotein S (SelS), which is an endoplasmic reticulum resident protein, is known to promote cell survival by regulating inflammation. Moreover, SelS has been shown to be responsive to ischemia in cultured astrocytes. A Finnish report revealed that a variation in the SelS gene locus is associated with a higher predisposition to ischemic stroke in humans, suggesting a crucial role for SelS in protection against brain ischemia. However, the time-course of SelS expression following cerebral ischemia in vivo remains unknown. In the present study, we show, for the first time, differential SelS expression from 3 h to 7 days after reperfusion in rats with transient focal cerebral ischemia induced by a 1-h middle cerebral artery occlusion. We found that the SelS protein level decreased in the ischemic core 3–7 days after reperfusion. Furthermore, SelS expression was upregulated in the ischemic penumbra adjacent to the ischemic core 3–7 days after reperfusion and is matched by reactive astrogliosis. Thus, we propose that the upregulation of Sels represents a reaction of astrocytes against inflammatory stimuli, and the findings of this study open a new chapter in the research of the interrelationships between SelS and cerebral ischemic stroke.