The Study On Treatment Of Histamine H₃ Receptor Antagonist To Rat Model With Intractable Epilepsy Of Infant Period And Toddler Age

Objective: To explore the anti-convulsion action of histamine inthe central system and treatment of histamine H3 receptor antagoniststo rat model with intractable epilepsy of infant period and toddler age.Methods: Wistar rat pups 12-day-old were used, which werereceived an intraperitoneal NMDA administration for 14 days to makeanimal model of intractable epilepsy of infant period and toddler age.88 Wistar rat pups 12-day-old were divided into three groupsrandomly and established normal control group, NMDA-inducedgroup and BH+NMDA group (this group was divided into 150mg/kggroup and 300mg/kg group according to the dose of BH). Wetherapied epileptic rats through injecting BH into stomach, and half toone hour later, rats were received an intraperitoneal NMDAadministration. The normal control group was treated with NS of thesame volume. The administration was performed from 8:30 to 10:00am daily for 14 days, and different doses were used in individual ageperiod according to response. The dose 15mg/kg of NS or NMDA toPN12~15, 30mg/kg to PN 16~18, 45mg/kg to PN19～20, 60mg /kg toPN21~23 and 75mg/kg to PN 24~25 rats were used once daily. Therat pups were observed for 2 hours after an administration. Latenciesand incidences to two NMDA-dependent stereotypical behaviors werenoted: tail twisting and emprosthotonus. Rats were sacrificed after twoor four weeks respectively. The histamine contents of each brainregion were determined with fluorimetry, and histamine H3 receptorswere evaluated with immunohistochemical method.Results: 3 to 5 minutes after NMDA administration, theautomatisms including chewing, head tremor, biting of paw or tail andtail twisting were observed in the NMDA-treated (12~17) -day-oldrats. Tail twisting was the most common behavior among theseautomatisms. Tail twisting involved tonic extension of tail withsuperimposed twirling movements. (12~17) -day-old rats experiencedlocomotor hyperactivity and ataxia of hindlimbs followed. Duringemprosthotonus seizures, the neck, spine, forelimbs and proximalhindlimbs (hips) were flexed, while the legs were extended at theknees. Overall, the pups resembled a curled ball or a fetal position.After emprosthotonus, all rats developed into tonic-clonic seizures.All of (12~13) -day-old rats and part of (14~17) -day-old ratsexperienced emprosthotonus. (18~25)-day-old rats became quietfollowing automatisms rather than emprothotonic. During the periodof systemic administration, latencies of tail twisting became longerand reached peak in 19-day-old rats. Then latencies began to decreasein 21-day-old rats, while became longer gradually to another peak in24-day-old rats. In contrast to NMDA-induced group, BH+NMDAgroup had longer latencies and lower incidences of tail twisting andemprothotonus. The differences of two groups became significantaccording to increase of dose of BH. On different phases ofpathogensis, we determined histamine content of cortex andhippocampus. The histamine contents of each brain region weresimilar between 2nd and 4th week. At 2nd week, histamine contents ofcortex and hippocampus of normal control group were 32.13±1.23ng/g and 30.48±2.11 ng/g respectively. Histamine contents of...