探討一氧化氮在幼鼠熱性痙攣中所扮演的角色

CNU IR > College of Smart Living > Dept. of Childhood Education and Nursery > MOST Project > Item 310902800/1840

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Title:	探討一氧化氮在幼鼠熱性痙攣中所扮演的角色 Studies of the Role Played by Nitric Oxide in the Development Febrile Seizure in Neonatal Rats
Authors:	林指宏 Jju-Home Lin
Contributors:	嬰幼兒保育系
Keywords:	一氧化氮熱性痙攣內毒素海馬迴兒童 Nitric oxide (NO) Febrile seizure Endotoxin Hippocampus Child
Date:	1998
Issue Date:	2008-07-18 16:08:16 (UTC+8)
Publisher:	台南縣：嘉南藥理科技大學嬰幼兒保育系
Abstract:	兒童罹患熱性痙攣(Febrile seizure)約有3-5%機率,而且其中約有1/3會再復發。雖然這是一個臨床常見的病症,然而我們對其相關之細胞和神經化學傳遞機轉所知相當有限。在眾多病因中,細菌感染和高燒一直被認為是主要的誘發因素。熱性痙攣與發燒和年齡有直接關連,長期研究發現熱性痙攣孩童或實驗動物其海馬迴容積或神經有明顯損傷現象,顯示熱性痙攣與海馬迴有直接關係。本實驗採用兩種不同之熱原(Lipopolysaccharide,LPS and interleukin-1.beta.,IL-1.beta.)分別誘導不同年齡層(5-15天)之幼鼠熱性痙攣現象。IL-1.beta.(1.mu.g/kg)誘導5-6天、7-8天、9-10天、11-12天、15天、21天大之幼鼠不同程度的熱性痙攣現象,年齡愈大誘導時間愈長(8-40分鐘),發作頻率愈少(40-0次/2小時內)。不同劑量之IL-1.beta.(1ng/kg、10ng/kg、100ng/kg、1.mu.g/kg、10.mu.g/kg)分別對7-8天大之幼鼠誘導不同程度之熱性痙攣現象,劑量愈高誘導時間愈短、發作頻率愈多。而此一痙攣現象受NMDA受體拮抗劑MK-801(10mg/kg)和APV(10mg/kg)、NOS抑制劑L-NAME(100mg/kg)、GABA受體拮抗劑Diazepam(5mg/kg)所減緩。但COX抑制劑Diclofenac(10mg/kg)和Aspirin (10mg/kg)反促使形成連續性痙攣現象,約30分鐘後導致實驗動物死亡,此一現象和對照組零死亡率有極明顯差異。採7-8天大幼鼠投與IL-1.beta.(10.mu.g/kg)12小時後犧牲進行海馬迴神經細胞內電生理記錄,得到連續自發性放電之類癲癇興奮電位,顯示此一熱性痙攣模式亦影響到中樞神經活性。本研究之結果提供一合適之人體熱性痙攣現象之動物研究模式,將有助於日後對熱性痙攣的機制討論模式。 Seizures induced by fever are the most prevalent age-specific seizures in infants and young children. Whether they result in long-term sequelae such as hippocampal neuronal loss and temporal lobe epilepsy is controversial. This study describes the establishment of a new animal model of febrile seizures using the infant rat. Febrile seizure was induced in pups by intraperitoneally administration of E. Coli lipopolysaccharide (1-10mg/kg) or administration of interleukin-1.beta. (1ng-10.mu.g/kg). The Pups seizures were determined by behavioral criteria such as scratching, face and body myoclonic twitches, forelimb clonus, chewing, tail-extensor, followed by tonic extensor or tonic-clonic convulsions, falling and rolling. Age-dependent (5-6, 7-8, 9-10, 11-12, 15, 21 days old rats) manners of febrile seizures induced by interleukin-1.beta. (1.mu.g/kg). In 7-8-old rats, the onset and tonic-clonic convulsions of interleukin-1.beta.-induced seizures varied markedly among individual animals. A dose-dependent febrile seizures induced by IL-1.beta. (1ng-10.mu.g/kg) were determined in 7-8-old rats. Twelve hours after IL-1.beta. (10.mu.g/kg), the pups were decapitated and the hippocampal slices were prepared. Spontaneous epileptiform activity in hippocampal neurons were obtained by conventional intracellular recording techniques. MK-801 (a potent NMDA-receptor blocker, 10mg/kg), APV (a NMDA-receptor blocker, 10mg/kg), L-NAME (a NOS inhibitor, 100mg/kg), or diazepam (a GABA-receptor blocker, 10mg/kg) inhibited febrile seizures induced by IL-1.beta. (1.mu.g/kg) when intraperitoneally 10 min before IL-1.beta. injection. However, Diclofenac (a COX inhibitor, 10mg/kg) and Aspirin (a COX inhibitor, 10mg/kg) produced pups status seizures and death when intraperitoneally 10 min before IL-1.beta. injection. In summary, an infant rat paradigm pyrogens-induced seizures which is suitable for long-term studies is described. This model should be highly valuable for studying the mechanisms and sequelae of febrile seizures.
Relation:	計畫編號:NSC87-2314-B041-014
Appears in Collections:	[Dept. of Childhood Education and Nursery] MOST Project

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