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N-Methyl-D-Aspartate-Induced Seizures In Wistar Developing Rats The Rudimentary Studying For The West Syndrome Model

Posted on:2005-01-24Degree:MasterType:Thesis
Country:ChinaCandidate:J T WangFull Text:PDF
GTID:2144360125950549Subject:Academy of Pediatrics
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OBJECTIVE: West syndrome which consists of tonic spasms,hapsarrhythmia and mental deficiency is an intractable epilepsy syndrome with age-specification. The majority of patients with WS suffer a poor outcome. Although the history of studying for it is over a century, there has been yet not a suitable animal model of West syndrome for carrying out the research. NMDA and /or its receptors are especially important about the establishment of epileptic animal model of the childhood because expression of NMDA receptors in an age-dependent fashion is related to the susceptibility to seizures. An appropriate model of WS in Velisek's article should involve: 1. Spontaneous seizures during relevant periods of postnatal development; 2. Seizures with spasms (flexions, extensions, or combination); 3. Diffuse nonspecific interictal EEG alterations; 4. Significant deterioration of the development of normal brain function; 5. Refractoriness to common AED therapy; 6. Certain response to treatment with adrenocorticotropic hormone (ACTH), corticosteroids, VPA, pyridoxine,γ-aminobutyric acid (GABA) ergic drugs (benzodjazepines,γ-vinyl-GABA) and some new AEDs such as FBM ; 7. It should be possible to induce this model in either normal or already compromised brain. In our study, we explore the behavioral manifestations and the ECoG (electrocorticogram) characteristics of the seizures induced by NMDA in Wistar rat pups, and discuss the possibility of establishment of an animal model of West syndrome. METHODS: Experiments were performed in 64 Wistar rat pups 12-day-old which were divided into two general groups randomly . Each general group consisted of 32 rat pups. The convulsant actions were observed in the first general group which included NMDA- treated group and the control group. Each group of 16 rats respectively was received an intraperitoneal injection with NMDA or NS. The administration was performed from 8:30 to 10:00 a.m. every day for 14 days, and different doses were used in individual age period according to response. The dose 15mg/kg of NS or NMDA in PN 12-15, 30mg/kg in PN18, 45mg/kg in PN18, 50mg/kg in PN19-20, 60mg/kg in PN21-23, 70mg/kg in PN 24-25 rats were used once daily. The rat pups were observed for 2 hours after an administration, the pattern of motor seizures and incidence, latencies as well as behavioral phenomena were evaluated and noted in the first general group. ECoG changes of the animal were observed in the second general group. 12-day-old rats were fixed and implanted electrodes under the sober situation in order that it might avoid the hit of anesthesia for the Wistar rat pups and the effect on ECoG recording. Spontaneous baseline ECoG was recorded for five minutes. Then the dose 15mg/kg of drug (or saline in controls) in the NMDA-treated group was administered i.p. and the ictal and interictal ECoG as well as ECoG of the ictal onset were recorded. RESULTS: The respect on the convulsant action, the automatisms including chewing, head tremor, biting of paw and tail, tail twisting observed in the NMDA-treated (12-13)-day-old rats, tail twisting was common among of these behaviors. (12-13)-day-old rats experienced locomotor hyperactivity and ataxia of hindlimb followed. Finally, emprosthotonic seizures which look like a ball may develop into clonic-tonic seizures in Wistar rat pups. At first, rat pups maintained emprosthotonus for several seconds only and repeated in several minutes; subsequently, the hyperflexion became prolonged gradually. The automatisms in the NMDA-treated group from 14-day-old rats to 25-day-old rats stop gradually to transform quiet, the emprosthotonus was not observed. During the systemic administration, incidence of tail twisting in Wistar rat pups: 100% in PN12-18, 86.7% in PN21, 66.7% in PN25; Incidence of emprosthotonus: 87.5% in PN12. Latency to onset of tail twisting in Wistar rat pups: it was short (976±218.34) in PN12, It reached peak (2586±338.68) in 18-day-old rats while in 21-day-old rats it began to decrease (2480±607.31) gradually. In the differ...
Keywords/Search Tags:N-Methyl-D-aspartate, Seizures, West syndrom Behavioral manifestations, Developing rats, Electrocorticogram recording
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