Abstract:

Abstract:Objective To explore the anti-convulsion action of histamine(HA) in the central system and treatment of histamine H₃ receptor(H₃R) antagonists to rat model with intractable epilepsy.Methods 88 Wistar rats (12-day-old) were randomly divided into three groups:normal control group,N-methyl-D-aspartate(NMDA) group and betahistine(BH) groups (including high and low dose BH groups).Wistar rats  received an intraperitoneal NMDA administration to make animal model of intractable epilepsy at infant period and toddler age.After that,the rats were observed daily for latencies and incidences to two NMDA-dependent stereotypical behaviors.The HA content of each brain region was determined with fluorimetry,and  H₃R were evaluated with immunohistochemical  method.Results The automatisms including tail twisting and emprosthotonus seizures of (12-17)-day-old rats were observed in NMDA and BH groups.The  rats,aged 18-25 d,became quiet following automatisms rather than emprothotonic.Compared with NMDA group,BH groups had longer latencies and lower incidences of tail twisting and emprosthotonus(P<0.05).At the end of the 2nd week,compared with normal control group,the HA contents of cortex and hippocampus in NMDA group were lower(P<0.05),and the expression rates of H₃R positive cells were higher(P<0.05).Compared with NMDA group,the HA contents of cortex and hippocampus in BH groups were higher(P<0.05),the expression rates of H₃R positive cells were decreased(P<0.05).At the end of the 4th week,the changes of HA contents between every two groups became less.There were significant differences of the HA contents between NMDA group and BH groups(P<0.05).But there were no significant differences of the expression rates of H₃R positive cells between every two groups(P>0.05).Conclusion The NMDA-induced model is similar to the clinical manifest of human West syndrome.It is up to animal model of intractable epilepsy at infant period and toddler age.The HA content of brain region is negatively related with seizure incidence.H₃R antagonists have certain therapeutic function to intractable epilepsy in rats at infant period and toddler age.

Key words: histamine;histamine H₃ receptor antagonist;intractable epilepsy;model,animal