Regulator of calcineurin 1 (Rcan1) has a protective role in brain ischemia/reperfusion injury

Background: an increase in intracellular calcium concentration [ca 2+] iis one of the first events to take place after brain ischemia. a key [ca 2+] i-regulated signaling molecule is the phosphatase calcineurin (cn),which plays important roles in the modulation of inflammatory cascades. here,we have analyzed the role of endogenous regulator of cn 1 (rcan1) in response to experimental ischemic stroke induced by middle cerebral artery occlusion.methods: animals were subjected to focal cerebral ischemia with reperfusion. to assess the role of rcan1 after stroke,we measured infarct volume after 48 h of reperfusion in rcan1 knockout (ko) and wild-type (wt) mice. in vitro studies were performed in astrocyte-enriched cortical primary cultures subjected to 3% oxygen (hypoxia) and glucose deprivation (hgd). adenoviral vectors were used to analyze the effect of overexpression of rcan1-4 protein. protein expression was examined by immunohistochemistry and immunoblotting and expression of mrna by quantitative real-time reverse-transcription polymerase chain reaction (real time qrt-pcr).results: brain ischemia/reperfusion (i/r) injury in vivo increased mrna and protein expression of the calcium-inducible rcan1 isoform (rcan1-4). i/r-inducible expression of rcan1 protein occurred mainly in astroglial cells,and in an in vitro model of ischemia,hgd treatment of primary murine astrocyte cultures induced rcan1-4 mrna and protein expression. exogenous rcan1-4 overexpression inhibited production of the inflammatory marker cyclo-oxygenase 2. mice lacking rcan1 had higher expression of inflammation associated genes,resulting in larger infarct volumes.conclusions: our results support a protective role for rcan1 during the inflammatory response to stroke,and underline the importance of the glial compartment in the inflammatory reaction that takes place after ischemia. improved understanding of non-neuronal mechanisms in ischemic injury promises novel approaches to the treatment of acute ischemic stroke. © 2012 sobrado et al; licensee biomed central ltd.