UM
The phosphodiesterase-4 inhibitor, FCPR16, attenuates ischemia-reperfusion injury in rats subjected to middle cerebral artery occlusion and reperfusion
Chen, Jiajia; Yu, Hui; Zhong, Jiahong; Feng, Hongfang; Wang, Haitao; Cheng, Yufang; Zou, Zhengqiang; Huang, Chang; Zhou, Zhongzhen; Zheng, Wenhua; Xu, Jiangping
2018-03
Source PublicationBRAIN RESEARCH BULLETIN
ISSN0361-9230
Volume137Pages:98-106
AbstractCurrent phosphodiesterase-4 (PDE4) inhibitors exert beneficial effects in central nervous system diseases via anti-inflammatory and anti-apoptotic properties, but many of them are plagued by side effects like nausea and emesis. FCPR16, a novel PDE4 inhibitor synthesized in our lab, has potential anti-inflammatory property. In the present study, we aimed to investigate the effects of FCPR16 in a rat model of ischemic stroke and evaluate its emetogenic potential. Our results showed that FCPR16 treatment improved neurological function, reduced cerebral infarct volume, and attenuated brain histological changes in rats subjected to middle cerebral artery occlusion and reperfusion (MCAO/R). Furthermore, levels of proinflammatory cytokines tumor necrosis factor a, interleukin-6 and interleukin-1 beta were decreased after FCPR16 treatment, as well as the ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein in MCAO/R rats. TUNEL staining and Western blot results showed that FCPR16 reduced apoptosis and regulated apoptotic-related proteins, with increased level of phosphorylated protein kinase B. Moreover, FCPR16 treatment increased cyclic adenosine monophosphate (cAMP) levels and cAMP-response element binding protein (CREB) phosphorylation in ischemic tissue. In addition, oral administration of 3 mg/kg FCPR16 did not cause vomiting in beagle dogs. This study indicates that FCPR16 has protective effects against cerebral ischemia-reperfusion injury through inhibiting inflammation and apoptosis via the cAMP/CREB pathway, while it has low emetogenic potential.
KeywordPDE4 inhibitor FCPR16 Ischemia-reperfusion injury Stroke Apoptosis Inflammation
DOI10.1016/j.brainresbull.2017.11.010
URLView the original
Indexed BySCI
Language英语
WOS Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
WOS IDWOS:000427344300011
PublisherPERGAMON-ELSEVIER SCIENCE LTD
The Source to ArticleWOS
Fulltext Access
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Cited Times [WOS]:7   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Recommended Citation
GB/T 7714
Chen, Jiajia,Yu, Hui,Zhong, Jiahong,et al. The phosphodiesterase-4 inhibitor, FCPR16, attenuates ischemia-reperfusion injury in rats subjected to middle cerebral artery occlusion and reperfusion[J]. BRAIN RESEARCH BULLETIN,2018,137:98-106.
APA Chen, Jiajia.,Yu, Hui.,Zhong, Jiahong.,Feng, Hongfang.,Wang, Haitao.,...&Xu, Jiangping.(2018).The phosphodiesterase-4 inhibitor, FCPR16, attenuates ischemia-reperfusion injury in rats subjected to middle cerebral artery occlusion and reperfusion.BRAIN RESEARCH BULLETIN,137,98-106.
MLA Chen, Jiajia,et al."The phosphodiesterase-4 inhibitor, FCPR16, attenuates ischemia-reperfusion injury in rats subjected to middle cerebral artery occlusion and reperfusion".BRAIN RESEARCH BULLETIN 137(2018):98-106.
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