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• W2334178760 endingPage "1308" @default.
• W2334178760 startingPage "1297" @default.
• W2334178760 abstract "Intense efforts are being undertaken to understand the pathobiology of ischemia and to develop novel and effective treatments. Angiotensin II type 2 receptor (AT2R) is related with a beneficial role in neurodegenerative disorders, including ischemia. However, the underlying molecular mechanism remains elusive. In this study, we have established that AT2R stimulation by C21 compound, a specific AT2R agonist, caused a VEGF upregulation. Using mouse primary cortical neurons exposed to oxygen–glucose deprivation (OGD), we established that this effect was mediated by a mechanism dependent of mTORC1 signaling since mTOR inhibition abolished the C21-induced VEGF upregulation. Also, we have temporally characterized the changes on VEGF levels after ischemia induction in rats using two different approaches: transient and permanent middle cerebral artery occlusion (tMCAO and pMCAO). VEGF levels were permanently augmented after reperfusion (tMCAO) whereas lower levels of VEGF were found after pMCAO, remarkably at 21 days. Therefore, C21 compound accelerated the recovery of the neurological status of pMCAO rats, reduced the ischemic damage area and abolished pMCAO-induced VEGF downregulation at 21 days. This effect of C21 compound was mainly observed in neurons of the peri-infarct area. Our results suggest that a C21-induced VEGF upregulation may be crucial after an ischemic neuronal insult in both of our experimental approaches. This upregulation was mediated by a mechanism dependent of Akt/mTOR signaling pathway, since mTOR inhibition abolished the VEGF upregulation induced by C21. Considering that VEGF is involved in regenerative processes, we propose that AT2R activation could be used as a potential pharmacological strategy after ischemic stroke." @default.
• W2334178760 created "2016-06-24" @default.
• W2334178760 creator A5019147942 @default.
• W2334178760 creator A5084027100 @default.
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• W2334178760 date "2016-07-01" @default.
• W2334178760 modified "2023-10-06" @default.
• W2334178760 title "Angiotensin II type-2 receptor stimulation induces neuronal VEGF synthesis after cerebral ischemia" @default.
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• W2334178760 doi "https://doi.org/10.1016/j.bbadis.2016.03.013" @default.
• W2334178760 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27045356" @default.
• W2334178760 hasPublicationYear "2016" @default.
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