The Role And Mechanism Of Rolipram In Early Brain Injury Following Experimental Subarachnoid Hemorrhage In Rats

PurposeRolipram is a specific phosphodiesterase-4 inhibitor which is traditionally used as an anti-depressant drug.Recent studies have demonstrated the neuroprotective effects of rolipram in several central nervous system insults.However,the role of rolipram in subarachnoid hemorrhage(SAH)remains unclear.The current study was aimed to investigate the role of rolipram in EBI after SAH and explore the potential mechanism.MethodsAdult male Sprague-Dawley rats were subjected to an endovascular perforation process to produce an SAH model.Animals were randomly divided into:sham group,sham+rolipram group,SAH+vehicle group,SAH+rolipram group.At 24 h after SAH,mortality,SAH grades,neurological function,brain edema was recorded.Western blotting was performed to assess the expression of SIRT1,ac-NF-?B,TNF-?,IL-1?,IL-6 and IL-10.Immunofluorescence staining was performed to evaluate the activation of microglia and the death of neuronal cells.ResultsAdministration of rolipram significantly ameliorated brain edema and alleviated neurological dysfunction after SAH.Rolipram treatment remarkably promoted the expression of Sirtuin 1(SIRT1)while inhibited acetylation of NF-?B.Moreover,rolipram significantly inhibited the activation of microglia as well as down-regulated the expression of pro-inflammatory cytokines TNF-?,IL-1?,and IL-6.In addition,rolipram increased the expression of protective cytokine IL-10.Furthermore,rolipram significantly alleviated neuronal death after SAH.ConclusionThese data suggested that rolipram exerts neuroprotective effects against EBI after SAH via suppressing neuroinflammation and reducing neuronal loss.The neuroprotective effects of rolipram were associated with regulating the SIRT1/NF-?B pathway.Rolipram could be a novel and promising therapeutic agent for SAH treatment.