| 摘要: | 我們的先前研究已知天麻能減少kainic acid （KA）誘發Spragrue-Dawley（SD）大鼠的癲癇發作，天 麻的這個作用與氧化自由基的抑制或生成有關。KA 注射6 週後在海馬區可以觀察到mossy fiber sprouting。KA 治療後會導致癲癇發作閾值降低，出現再發性的癲癇發作，這種癲癇發作類似人類mesial temporal lobe epilepsy，主要的病理變化在海馬區。KA 誘發癲癇發作的腦損傷在齒狀核會出現sprouting of mossy fiber，而人類頑固性癲癇小孩死後的組織也有相似的組織再生。選擇性海馬區神經細胞的損 傷和mossy fiber sprouting 可以作為癲癇形成和自發性癲癇發作產生的原因。顳葉性癲癇有海馬硬化 （temporal lobe epilepsy with hippocampal sclerosis）的患者其海馬區有嚴重的神經細胞喪失，astrogliosis 和mossy fiber sprouting，如此推測海馬區域神經細胞的喪失隨後進行性mossy fiber sprouting 可以是提 供癲癇形成（epileptogenesis）的重要因素。S100B 是astrocyte 的細胞外分泌物，而astrocytes 藉著S100B 來調節神經活動。Neuropeptide Y（NPY）在癲癇發作過渡興奮的情況（condition of hyperexcitability） 下扮演調節海馬功能的角色，而gamma-aminobutyric acid （GABA）是一種抑制性的神經傳導物質。 因此，本研究的目的在探討天麻對KA 誘發癲癇病灶形成的預防。首先，使用KA（12 mg/kg）於SD 大鼠腹腔注射誘發癲癇發作，6 週將大鼠犧牲取腦，觀察海馬區的組織結構、Glial fibrillary acid protein （GFAP）、S100B、GABAA、NPY 和NeuN 陽性染色細胞，以及mossy fiber sprouting，藉此變化推測 天麻對癲癇病灶形成的預防；其次，觀察天麻預防癲癇病灶形成activator-protein 1（AP-1）所扮演的 角色。本研究分二年進行如下：第一年：癲癇病灶形成動物模型的建立，以及天麻對KA 誘發癲癇病 灶形成之效用；第二年：AP-1 在天麻減低KA 誘發癲癇病灶形成之角色。 預期完成本研究成果可以提供天麻預防癲癇病灶形成的科學證據，如此對癲癇的治療和預防做出 貢獻。
Our previous studies have known that Gastrodia elata (GE) can reduce epileptic seizures induced by kainic acid (KA), and these effect of GE result from its suppressive and scavenging effect of oxygen free radicals generation.We also find that mossy fiber sprouting generates in the hippocampus region 6 weeks after KA administration. The threshold decreases and became to repeat seizures after KA administration, and this seizure is similar to mesial temporal lobe epilepsy in human because the main pathological changes in the hippocampus. KA-induced brain damage results in generation of mossy fiber sprouting in the dentate gyrus of hippocampus, and that is similar to the reorganization in death child with intractable epilepsy. The etiology of epileptogenesis and spontaneous epileptic seizure results from selective neuronal damage and mossy fiber sprouting in the hippocampus region. Because severe loss of neuronal cells, astrogliosis and mossy fiber sprouting in the hippocampus region in temporal lobe epilepsy patients with hippocampal sclerosis , suggestive that neuronal loss of hippocampus following mossy fiber sprouting may provide an important factor of epileptogenesis. S100B is an extracellular substance that is secreted from astrocytes, and that plays a regular role of neuronal activity. The neuropeptide Y (NPY) plays a regular function role in hippocampus when epileptic seizures induce a condition of hyperexcitability, whereas the gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter. Therefore, the present study is to investigate the effect of GE on the prevention of epileptic focus formation: first, intra-abdominal administration of KA (12 mg/kg) induced epileptic seizures in Spragrue-Dawley (SD) rats, and the rats were sacrificed and the brain was removed 6 weeks after KA administration. The morphology changes, glial fibrillary acid protein (GFAP), S100B, GABAA, NPY and NeuN immunoreactive cells and mossy fiber sprouting were observed in the hippocampus, according to the changes to explain the effect of GE on formation of epileptic focus; second, we observed the role of activator protein 1 (AP-1) in the prevention of GE for epileptic focus formation. The present study divided into the two years as follows: first year, the animal model establishment of epileptic focus formation, and the effect of GE on the formation of epileptic focus induced by KA; second year, the role of AP-1 in GE reducing the formation of epileptic focus. We expects the results of the present study may provide a scientific evidence of GE in the prevention of epileptic focus formation, thus, the results of the present study will contribute to epileptic treatment and prevention. |
