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The present study investigated whether repeated treatment with the PDE4 inhibitor roflumilast rescued memory loss and attenuated neuroinflammation in rats following transient global cerebral ischemia (TGCI). TGCI caused memory impairments, neuronal loss (reflected by Neuronal nuclei (NeuN) immunoreactivity), and compensatory neurogenesis (reflected by doublecortin (DCX) immunoreactivity) in the hippocampus. Also, increases in the protein expression of the phosphorylated response element\u2010binding protein (pCREB) and inflammatory markers such as the glial fibrillary acidic protein (GFAP) and ionized calcium\u2010binding adaptor molecule 1 (Iba\u20101), were detected in the hippocampus in TGCI rats. Repeated treatment with roflumilast (0.003 and 0.01\u00a0mg\/kg) prevented spatial memory deficits without promoting hippocampal protection in ischemic animals. Roflumilast increased the levels of pCREB, arginase\u20101, interleukin (IL) 4, and IL\u201010 in the hippocampus 21\u00a0days after TGCI. These data suggest a protective effect of roflumilast against functional sequelae of cerebral ischemia, which might be related to its anti\u2010inflammatory properties.<\/jats:p>","DOI":"10.1111\/ejn.15089","type":"journal-article","created":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T14:35:11Z","timestamp":1608388511000},"page":"1171-1188","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Roflumilast protects against spatial memory impairments and exerts anti\u2010inflammatory effects after transient global cerebral ischemia"],"prefix":"10.1111","volume":"53","author":[{"given":"J\u00e9ssica M.","family":"Bonato","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Therapeutics State University of Maring\u00e1 Maring\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics State University of Maring\u00e1 Maring\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia S. 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