The Rudimentary Study Of Traditional Anti-epileptic Drugs On The Treatment Of The West Syndrome Model

OBJECTIVE: With intraperitoneal N-methyl-D-asprtate(NMDA; 15-75mg/kg) administration, we attempted to establish amodel of West syndrome and by the anti-epileptic effects oftraditional anticonvulsant drugs, we want to test the extent ofconvulsions induced by NMDA conform to human′s West syndrome.METHODS: Experiments were performed in 80 Wistar ratpups 12-day-old which were divided into four general groupsrandomly,and established normal control group, NMDA-treatedgroup, CBZ+NMDA group and PB+NMDA group, two drugs usedin clinical neurology to treat epilepsy were tested against theNMDA-induced seizures. CBZ (100mg/kg) and PB (30mg/kg) wereused for the pretreatment of PN12 rats. two drugs were dailydissolved in NS and administrated intragastrically (i. g.) 30 minutesbefore the NMDA challenge. The rats of normal control group andNMDA-treated group were pretreated with equal volumes of NS (i.g.). All groups were received an intraperitoneal (i. p.) injection withNMDA or NS respectively .The administation was performed from8:30 to 10:00 a. m. everyday for 14 days, and different doses wereused in individual age period according to pilot experiment andprevious reports .The dose 15mg/kg of NS or NMDA in PN12-15;30 mg/kg in PN16-18; 45 mg/kg in PN19-20; 60 mg/kg in PN21-23;75 mg/kg in PN24-25 rats were used once daily. NMDA were dailydissolved in NS 2 hours before administration. The rat pups wereobserved for 2 hours after an administration ,the pattern of motorseizures and incidence, latency of seizures (tail-twisting andemprosthotonus) were evaluated and noted in all groups. Todetermine whether the pretreatment may result in short-termalteration of serum and long-term alterations of brain, rats of allgroups were killed in PN19,PN26,PN40 respectively, thendetermine serum neuron-specfic enolase (NSE) concentration bymeans of bi-antibody ELISA, abnormal mossy fiber sprouting (MFS)was observed in the inner molecular layer of the dentate gyrus andthe pyramidal cell layer of the CA3 section of the hippocampus byTimm histochemical staining. RESULTS: There were no abnormal changes in the behavior ofdrug-pretreated groups after 30 minutes administration (i.g.).NMDA-treated group, CBZ+NMDA group and PB+NMDA groupfirst induced behavior arrests, then automatisms appeared, inducingchewing,head tremor,biting of paw,tail and other rats, tail twistingobserved in the NMDA-treated group and drug-pretreated groups,(12-17) -day-old rats experienced locomotor hyperactivityand ataxiaof hindlimb followed. Finally, emprosthotonus seizures which looklike a ball may develop into clonic-tonic seizures in wistar rat pups.At first, rat pups maintained emprosthotonus for several secondsonly and repeated in several minutes; subsequently, the hyperflexionbecome prolonged gradually. The automatisms in NMDA-treatedgroup, CBZ+NMDA group and PB+NMDA group stop gradually totransform quiet and the emprosthotonus was not observed from18-day-old to 25-day-old rats. latency to onset of tail twisting:latency of NMDA-treated group reach peak (1604±470.68), while in21-day-old rats it began to decrease (1118±432.60), it increase in25-day-old rats obviously (3030±2692.28), trends of twodrug-pretreated groups are similar to NMDA-treated group, CBZincreased the latency to onset of tail-twisting in PN12-13significantly (P<0.05), while PB increased the latency to onset oftail-twisting in PN12-16 significantly (P<0.05), CBZ and PBdecreased the incidence of emprosthotonus in PN16 significantly(P<0.05), there was no obvious difference in other days comparedwith NMDA-treated group (P﹥0.05). The serum NSE concentrationof NMDA-treated model group were 24.379±3.001ug/l,21.019±1.771ug/l, 17.345±1.888ug/l in 1st, sec and 4th weekrespectively. with time going ,rate and degree of seizure paralleledwith NSE. CBZ and PB significantly decreased the level of serumNSE in 1st and sec week (P<0.05), and compared with normalcontrol group, the level of NSE all increased significantly (P<0.05).Observing the pathology transformation of rat′s brain undermicroscope, abnormal MFS observed in all NMDA-treated groupsbecome more and more severe, scales were all 0 in the 1st week,scales of NMDA-treated model group were 0.25±0.46, 1.70±0.82 insec and 4th week separately, scale of CBZ+NMDA group were...