Effects Of PDE4 Inhibitor On Cognitive Impairments Induced By Status Epilepticus And The Mechanism In The Immature Brain

PART I EFFECTS OF PDE4 INHIBITOR ON COGNITIVE IMPAIRMENTS INDUCED BY STATUS EPILEPTICUS IN THE IMMATURE BRAINObjective To research the effects of PDE4 inhibitor on cognitive impairments induced by status epilepticus in the immature brain.Methods Seventy-two P21 SD male rats were randomly divided into four groups,there were N+Vehicle, N+Rolipram, SE+Vehicle and SE+Rolipram, and we used Licl-Pilo 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.Results Compared to the (N+Vehicle) group, In the Morris water maze test, the (SE+vehicle) group’s escaping latency period were significantly longer (the third day and fourth day were P<0.01 and P<0.05);the time in the target quadrant were 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 were shorter (P<0.001); and all of this were rescued with Rolipram treatment. Compared to the (SE+Vehicle) group, In the Morris water maze test, the (SE+Rolipram) group’s escaping latency period were significantly shorter (the fourth day was P<0.05); the time in the target quadrant were 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 were longer (P<0.01).Conclusion These results indicate that the PDE4 inhibitor Rolipram rescues cognitive impairments after SE.PART II THE MECEANISM OF PDE4 INHIBITOR ON COGNITIVE IMPAIRMENTS INDUCED BY STATUS EPILEPTICUS IN THE IMMATURE BRAINObjective To research the mechanism of PDE4 inhibitor on cognitive impairments induced by status epilepticus in the immature brain.Methods One hundred and seven P21 SD male rats were randomly divided into four groups, there were N+Vehicle, N+Rolipram, SE+Vehicle and SE+Rolipram, and we used Licl-Pilo to build the SE model. The animals eceived vehicle (5%DMSO) or Rolipram (0.03 mg/kg) once a day (ip) for two week. The cAMP levels were evaluated by Elisa; the pCREB and CREB levels were evaluated by western blotting; hippocampus long-term potentiation was evaluated by Patch Clamp Technique. Results Compared to the (N+Vehicle) group, In the Elisa test cAMP levels were decreased (P<0.05); In the western blotting test pCREB levels were decreased (P<0.001); long-term potentiation was reduced (P<0.05),and all of this were rescued with Rolipram treatment. Compared to the(SE+Vehicle) group, the (SE+Rolipram) group’s in the Elisa test the cAMP levels were increased (P<0.05); In the western blotting test pCREB levels were increased (P<0.001); long-term potentiation was rescued (P<0.05).Conclusion These results indicate that the PDE4 inhibitor Rolipram rescues cognitive impairments after SE, and this may be mediated through increased CREB activation during learning.