| 摘要: | 因為發燒所引起的熱性痙攣 (febrile seizure, FS)是好發於三月齡至五歲齡的兒童常見的疾病，其復發率將近30%，其中有2-3％病童將來極有可能發展成癲癇病患。然而目前的研究對於熱性痙攣所造成的後遺症，如海馬迴神經損傷或顳葉性癲癇是否為真仍存在著爭議。本實驗以幼鼠為新的熱性痙攣動物疾病探討模式，直接採用熱原乙型第一介白質 (Interleukin-1b, IL-1β)分別誘導不同日齡的幼鼠熱性痙攣現象。以IL-1β (1 mg/kg)腹腔注射7, 14, 21, 28日齡的幼鼠後，觀察其熱性痙攣行為，發現隨著幼鼠日齡的增加，痙攣發作的誘發時間越長，發作的頻率也相對的減少。而7日齡的幼鼠在 IL-1β誘發的痙攣模式中的行為分級表現較其他日齡更明顯。IL-1β誘導的痙攣現象可受事先投與NMDA受體拮抗劑MK-801 (10 mg/kg)和APV (10 mg/kg)，NOS抑制劑L-NAME (100 mg/kg)、GABA受體拮抗劑diazepam (5 mg/kg)或dexamethasone (5 mg/kg)所減緩；而腦內的一氧化氮濃度與IL-1β亦呈劑量依賴效應，事先投與上述藥物則不僅可減少腦內一氧化氮的濃度，也延長IL-1β痙攣誘發時間及減少痙攣發作頻率。本實驗以IL-1β誘發幼鼠熱性痙攣動物疾病模式不僅造成幼鼠體溫上升，且痙攣發作行為分層明顯，與臨床上觀察相似，證明了一氧化氮參與熱性痙攣發作的關連性。
Febrile seizure or febrile convulsion, an event induced by fever, is the most prevalent age-specific form of seizure in infants and young children, and usually occurs between the ages of 3 months to 5 years. The recurrence rate is about 30% and approximately 2-3% of suffering children are likely to become epilepsy in the future. However, febrile seizures result in immediate or latent sequelae such as hippocampal neuronal loss and temporal lobe epilepsy is still a subject of controversy. This study provides a new animal model of febrile seizures using the infant rat. Febrile seizures were induced in 7, 14, 21, and 28-day-old rats by intraperitoneal administration of interleukin-1β (IL-1b, 1 μg/kg). In this manner, differences in pups’ seizures could be noted according to their differing stages of development. The most pronounced effect was found in 7-day-old rats, where the onset of IL-1β-induced seizures and tonic/clonic convulsions far surpassed those found in other age groups. Dose-dependent febrile seizures induced by IL-1β (1 ng/kg-10 mg/kg) were also determined in 7-day-old rats. Pretreament of MK-801 (a potent NMDA-receptor blocker, 10 mg/kg), APV (a NMDA-receptor blocker, 10 mg/kg), L-NAME (a NOS inhibitor, 100 mg/kg), dexamethasone (10 mg/kg) and diazepam (a GABA-receptor blocker, 10 mg/kg) were found to inhibit febrile seizures onset time, seizures severity and also reduced the brain nitric oxide production and levels. The data suggested that nitric oxide mayb play an important role in febrile seizure development. |
