Effect Of OREXIN Receptors On The Epilepsy Following Sleep Deprivation

ObjectiveTo investigate the effects of orexin receptor on the behaviour,hippocampal histopathology and cell proliferation in the pentylenetetrazol (PTZ)-induced epileptic rats after sleep deprivation.MethodsForty-eight male wistar rats weighing 200～250g were randomly divided into six groups: control group (CC); PTZ; sleep deprivation followed by PTZ (SD+PTZ); sleep deprivation followed by PTZ and DMSO (SD+PTZ+DMSO); pretreatment with orexin-1 receptor(OX1R)antagonist SB334867 followed by sleep deprivation and PTZ (SD+ PTZ+SB) and pretreatment with orexin-2 receptor (OX2R)antagonist TCS OX2 29 followed by sleep deprivation and PTZ(SD+PTZ+TCS) rats of group CC were raised under the same conditions as well as other group; PTZ group received intraperitoneal injection of 50mg/kg induced seizures; sleep deprivation using modified multiple platform model of sleep deprivation set up the model. Group SD+PTZ were intraperitoneally administrated a convulsive dose of pentylenetetrazol (PTZ, 50mg/kg) following sleep deprivation; groups SD+PTZ+DMSO,SD+PTZ+SB和SD+PTZ+TCS were intracerebro- ventricular injection of solvent control DMSO,OX1R antagonist SB334867,OX2R antagonist TCS OX2 29 respectively as well as sleep deprivation,then the rats were intraperitoneally administrated a convulsive dose of pentylenetetrazol (PTZ, 50mg/kg). The behaviour compose of latent period,duration,grade score and death percent were observed.After 6days following PTZ-induced seizures bromodeoxyuridine(BrdU)was intraperitoneal injection to mark the cell in proliferation, 12hours later again, and24hours later.animals were put to death to take the sample, hippocampal histopathology and cell proliferation of the PTZ-induced epileptic rats were observed among different groups.ResultsThe behaviour in SD rats was appeared to be shorter latency, longer duration and greater intensity of seizure induced by PTZ, with an increase in percentage of death as compared with control rats. We also investigated the hippocampal neurons and cell proliferation with BrdU in the dentate gyrus using immunofluorescence technique. The treatment with SD led to a serious damage of neurons in the CA3 of the hippocampus and a significant increase in the number of BrdU positive-cells in the hilus and the subgranular zone (SGZ) of the dentate gyrus after PTZ-induced seizures. However, intraventricular (i.c.v) administration of orexin-1 antagonist SB-334867(30nmol/kg) or orexin-2 antagonist TCS OX2 29(30nmol/kg)remarkably blocked the affection of SD on the PTZ-induced seizures. Especially, the effect of orexin-2 antagonist on the PTZ-induced seizures was shown to be stronger than that of orexin-1 antagonist.ConclusionThese results suggest that the orexin receptor antagonists may attenuate the adverse effect of SD on the PTZ-induced seizures, at least in part, via the reduction of the neuronal cell damage in the CA3 of the hippocampus and the inhibition of cell proliferation in the dentate gyrus. It may be thought as a mechanim that SD affects epilepsy.