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Here, gene expression profiles of datasets GSE160500 and GSE97537 were downloaded from the GEO database, which were related to ischemic stroke in rats. Olfactory receptor 78 (Olfr78) was screened, and which highly associated with Calcium signalling pathway and MAPK pathway. Interacting protein of Olfr78, Prkaca, was predicted by STRING, and their interaction was validated by Co\u2010IP analysis. Then, a rat model of middle cerebral artery occlusion\/reperfusion (MCAO\/R) and a neuronal cell model stimulated by oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R) were constructed, and the results showed that expression of Olfr78 and Prkaca was downregulated in MCAO rats and OGD\/R\u2010stimulated neurons. Overexpression of Olfr78 or Prkaca inhibited the secretion of inflammatory factors, Ca<jats:sup>2+<\/jats:sup> overload, and OGD\/R\u2010induced neuronal apoptosis. Moreover, Overexpression of Prkaca increased protein levels of cAMP, PKA and phosphorylated p38 in OGD\/R\u2010stimulated neurons, while SB203580, a p38 inhibitor, treatment inhibited activation of the cAMP\/PKA\u2010MAPK pathway and counteracted the effect of Olfr78 overexpression on improvement of neuronal functions. Meanwhile, overexpression of Olfr78 or Prkaca markedly inhibited neuronal apoptosis and improved brain injury in MCAO\/R rats. In conclusion, overexpression of Olfr78 inhibited Ca<jats:sup>2+<\/jats:sup> overload and reduced neuronal apoptosis in MCAO\/R rats by promoting Prkaca\u2010mediated activation of the cAMP\/PKA\u2010MAPK pathway, thereby improving brain injury in cerebral ischaemia\u2013reperfusion.<\/jats:p>","DOI":"10.1111\/jcmm.18366","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T14:34:34Z","timestamp":1718030074000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Overexpression of olfactory receptor 78 ameliorates brain injury in cerebral ischaemia\u2013reperfusion rats by activating Prkaca\u2010mediated <scp>cAMP<\/scp>\/<scp>PKA\u2010MAPK<\/scp> pathway"],"prefix":"10.1111","volume":"28","author":[{"given":"Tao","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Neurology Shaanxi Provincial People's Hospital  Xi'an 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