Effects of Rolipram on cognitive impairments induced by epilepticus status in the immature brain

Abstract:

Objective：To explore the effects of Rolipram on cognitive impairments induced by epilepticus status in the immature brain. Methods：Ninety six P21 SD male rats were randomly divided into four groups：N+Vehicle（N+Veh），N+Rolipram（N+Ro），SE+Vehicle（SE+Veh） and SE+Rolipram（SE+Ro）. Licl-Pilo was used to build the SE model. The animals received vehicle（5% DMSO） or Rolipram（0.03 mg/kg） once a day（ip） for two week. The cognitive functions were tested by Morris water maze，step-through test and hippocampus long-term potentiation；the phosphorylated cAMP response element binding protein（pCREB） levels were evaluated by Western blot. Results：Compared with those of （N+Vehicle） group，in the Morris water maze test，the（SE+vehicle） group’s escaping la－tency period was significantly longer（the third day and fourth day：P<0.01 and P<0.05）；the time in the target quadrant was longer in probe trail（P<0.01），cross-platform times were decreased（P<0.05）；in the step-through test，the（SE+vehicle） group’s escape latency was shorter（P<0.001）；the slop of fEPSP in hippocampus long-term potentiation was reduced at 30 min after HFS（P<0.05）；in Western blot test，pCREB levels were decreased（P<0.001）；and all of these were rescued with Rolipram treatment. Compared with those of （SE+Vehicle） group，in the Morris water maze test，the（SE+Rolipram） group’s escaping latency period was significantly shorter（the fourth day：P<0.05）；the time in the target quad－rant was shorter in probe trail（P<0.05），cross-platform times were increase（P<0.05）；in the step-through test，the（SE+Rolipram） group’s escape latency was longer（P<0.01）；the slop of fEPSP in hippocampus long-term potentiation was increased at 30min after HFS（P<0.01）；in Western blot，pCREB levels were in－creased（P<0.01）. Conclusion：These results indicate that the PDE4 inhibitor rolipram rescues cognitive impairments after SE，and this may be mediated through increased pCREB levels.