前言
自發(fā)性遺傳模型為研究癲癇全身性發(fā)作，特別是研究癲癇失神發(fā)作提供了基礎(chǔ)。WAG/Rij大鼠用于研究遺傳性癲癇失神發(fā)作，其行為學(xué)改變、EEG表現(xiàn)（表現(xiàn)為棘慢復(fù)合板波）以及遺傳特性等方面與人類癲癇失神發(fā)作極為相像，已被廣泛用于研究人類癲癇失神發(fā)作。
部分造模方法
使用動物：大鼠
【造模機制】：
WAG/Rij大鼠來源于1924年Bacharach培育的遠交系Wistar基因突變大鼠。
【模型特點】：
目前常用的失神發(fā)作遺傳模型主要為WAG/Rij大鼠，無論是在清醒或睡眠狀況下，均能記錄到雙側(cè)同步、陣發(fā)性的棘波發(fā)放和兩側(cè)同步對稱的3Hz棘慢波發(fā)放(spike and wave discharges,SWDs)，同時伴有臨床失神發(fā)作的表現(xiàn)。
【模型評估和應(yīng)用】：
能顯著抑制該模型失神發(fā)作的藥物往往對臨床失神發(fā)作有效，兩者間具有高度相關(guān)性。g－氨基丁酸B1激動劑能加重WAG/Rij大鼠模型的SWDs發(fā)放。盡管上述兩種遺傳性失神模型具有自發(fā)失神發(fā)作及SWDs，但因難以大量繁殖，從而使其應(yīng)用受到限制。
參考文獻：
1.Andrè V, Dube C, Francois J, et al. Pathogenesis and pharmacology of epilepsy in the lithium-pilocarpine model. Epilepsia,2007,48 (Suppl 5):41-47
2.Gareri P, Condorelli D, Bellua.rdo N, el al. Antiabsence effects of carbenoxolone in two genetic animal models of absence epilepsy (WAG/Rij rats and lh/lh mice).Neuropharmacology, 2005, 49 (4):551-563
3.Holmes GL. Animal model studies application to human patients. Neurology, 2007, 69 (24 Suppl 3): S28-32
4.Jefferys JG. Models and mechanisms of experimental epilepsies. Epilepsia, 2003, 44 (Suppl 12):44-50
5.Löscher W,Leppik IE. Critical re-evaluation of previous preclinical strategies for the cliscovery and the development of new anliepileplic drugs. Epilepsy Res, 2002, 50 (1-2):17-20
6.Löscher W,Schmidt D.Stralegies in aatiepileptic drug development: is rational drug design superior to random screening and structural variation?Epilepsy Res, 1994, 17 (2):95-134
7.Wang Y, Zhou D, Wang B, el al. A kindling model of pharmacoresislanl temporal lobe epilepsy in SpragueDawley rats induced by Coriaria lactone and its possible mechanism. Epilepsia,2003,44(4):475-488
8.White HS. Preclinical development of antiepileptic drugs: past, present, and future directions. Epilepsia, 2003, 44 (Suppl 7):2-8
號二維碼.jpg)
