PMID- 26998028 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1792-0981 (Print) IS - 1792-1015 (Electronic) IS - 1792-0981 (Linking) VI - 11 IP - 3 DP - 2016 Mar TI - Rolipram stimulates angiogenesis and attenuates neuronal apoptosis through the cAMP/cAMP-responsive element binding protein pathway following ischemic stroke in rats. PG - 1005-1010 AB - Rolipram, a phosphodiesterase-4 inhibitor, can activate the cyclic adenosine monophosphate (cAMP)/cAMP-responsive element binding protein (CREB) pathway to facilitate functional recovery following ischemic stroke. However, to date, the effects of rolipram on angiogenesis and cerebral ischemia-induced neuronal apoptosis are yet to be fully elucidated. In this study, the aim was to reveal the effect of rolipram on the angiogenesis and neuronal apoptosis following brain cerebral ischemia. Rat models of ischemic stroke were established following transient middle cerebral artery occlusion and rolipram was administered for three, seven and 14 days. The results were examined using behavioral tests, triphenyl tetrazolium chloride staining, immunostaining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) to evaluate the effects of rolipram therapy on functional outcome, angiogenesis and apoptosis. Western blot analysis was used to show the phosphorylated- (p-)CREB protein level in the ischemic hemisphere. The rolipram treatment group exhibited a marked reduction in infarct size and modified neurological severity score compared with the vehicle group, and rolipram treatment significantly promoted the microvessel density in the ischemic boundary region and increased p-CREB protein levels in the ischemic hemisphere. Furthermore, a significant reduction in the number of TUNEL-positive cells was observed in the rolipram group compared with the vehicle group. These findings suggest that rolipram has the ability to attenuate cerebral ischemic injury, stimulate angiogenesis and reduce neuronal apoptosis though the cAMP/CREB pathway. FAU - Hu, Shouye AU - Hu S AD - Department of Osteonecrosis and Joint Reconstruction, Xi'an Honghui Hospital, Xi'an, Shaanxi 710068, P.R. China; Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710068, P.R. China. FAU - Cao, Qingwen AU - Cao Q AD - Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710068, P.R. China. FAU - Xu, Peng AU - Xu P AD - Department of Osteonecrosis and Joint Reconstruction, Xi'an Honghui Hospital, Xi'an, Shaanxi 710068, P.R. China; Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710068, P.R. China. FAU - Ji, Wenchen AU - Ji W AD - Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710068, P.R. China. FAU - Wang, Gang AU - Wang G AD - Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710068, P.R. China; Department of Neurosurgery, Shaanxi Province People's Hospital, Xi'an, Shaanxi 710068, P.R. China. FAU - Zhang, Yuelin AU - Zhang Y AD - Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710068, P.R. China; Department of Neurosurgery, Shaanxi Province People's Hospital, Xi'an, Shaanxi 710068, P.R. China. LA - eng PT - Journal Article DEP - 20151229 PL - Greece TA - Exp Ther Med JT - Experimental and therapeutic medicine JID - 101531947 PMC - PMC4774329 OTO - NOTNLM OT - angiogenesis OT - cAMP/cAMP-responsive element binding protein pathway OT - neuronal apoptosis OT - rat OT - rolipram EDAT- 2016/03/22 06:00 MHDA- 2016/03/22 06:01 PMCR- 2015/12/29 CRDT- 2016/03/22 06:00 PHST- 2014/02/04 00:00 [received] PHST- 2014/06/13 00:00 [accepted] PHST- 2016/03/22 06:00 [entrez] PHST- 2016/03/22 06:00 [pubmed] PHST- 2016/03/22 06:01 [medline] PHST- 2015/12/29 00:00 [pmc-release] AID - ETM-0-0-2958 [pii] AID - 10.3892/etm.2015.2958 [doi] PST - ppublish SO - Exp Ther Med. 2016 Mar;11(3):1005-1010. doi: 10.3892/etm.2015.2958. Epub 2015 Dec 29.