کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8838985 1613220 2018 28 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The phosphodiesterase-4 inhibitor, FCPR16, attenuates ischemia-reperfusion injury in rats subjected to middle cerebral artery occlusion and reperfusion
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
The phosphodiesterase-4 inhibitor, FCPR16, attenuates ischemia-reperfusion injury in rats subjected to middle cerebral artery occlusion and reperfusion
چکیده انگلیسی
Current 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 α, interleukin-6 and interleukin-1β 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research Bulletin - Volume 137, March 2018, Pages 98-106
نویسندگان
, , , , , , , , , , ,