2024-03-28T09:17:08Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/65232023-10-27T12:48:16Zcom_20.500.12105_2060com_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_2145com_20.500.12105_2144col_20.500.12105_2061col_20.500.12105_2146
Repisalud
author
Sobrado, Monica
author
Ramirez, Belen G.
author
Neria, Fernando
author
Lizasoain, Ignacio
author
Arbones, Marie Lourdes
author
Minami, Takashi
author
Redondo, Juan Miguel
author
Moro, Maria Angeles
author
Cano, Eva
funder
Instituto de Salud Carlos III
funder
Ministerio de Ciencia e Innovación (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
2018-10-25T08:19:46Z
2018-10-25T08:19:46Z
2012
J Neuroinflammation. 2012; 9(1):48
1742-2094
http://hdl.handle.net/20.500.12105/6523
22397398
10.1186/1742-2094-9-48
Journal of Neuroinflammation
Background: An increase in intracellular calcium concentration [Ca2+](i) is one of the first events to take place after brain ischemia. A key [Ca2+](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.
eng
Calcineurin
Calcium
Glia
Hypoxia
Inflammation
Rcan1
Stroke
SYNDROME CRITICAL REGION-1
DOWN-SYNDROME
CEREBRAL-ISCHEMIA
T-CELLS
PHOSPHATASE CALCINEURIN
OXIDATIVE STRESS
GENE-EXPRESSION
UP-REGULATION
NEURAL CELLS
ASTROCYTES
Regulator of calcineurin 1 (Rcan1) has a protective role in brain ischemia/reperfusion injury
journal article
URL
https://repisalud.isciii.es/bitstream/20.500.12105/6523/1/RegulatorOfCalcineurin1Rcan1_2012.pdf
File
MD5
cda94f5d006479c7d1bceeee84551f64
1243695
application/pdf
RegulatorOfCalcineurin1Rcan1_2012.pdf
URL
https://repisalud.isciii.es/bitstream/20.500.12105/6523/4/RegulatorOfCalcineurin1Rcan1_2012.pdf.txt
File
MD5
7199c2ebfd40c3cccfcd0125badd7665
60253
text/plain
RegulatorOfCalcineurin1Rcan1_2012.pdf.txt