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實驗性自身免疫性腦脊髓炎模型(EAE模型)

更新時間:2024-08-06點(diǎn)擊次數(shù):555

實驗性自身免疫性腦脊髓炎模型(EAE模型)

背景簡介:

多發(fā)性硬化癥(Multiple Sclerosis,MS)是一種發(fā)生于中樞神經(jīng)系統(tǒng)的炎癥性脫髓鞘疾病。實驗性自身免疫性腦脊髓炎模型(Experimental Autoimmune Encephalomyelitis,EAE)是研究該疾病的基本模型。EAE模型實驗動物通過神經(jīng)組織(其中的某些成分)或病毒誘導(dǎo)產(chǎn)生的。EAE的誘導(dǎo)有主動誘導(dǎo)法和被動誘導(dǎo)法兩種。不同的免疫方法,可影響抗原遞呈,激發(fā)不同的免疫反應(yīng),這不但影響EAE的發(fā)生率,還可影響其發(fā)展與轉(zhuǎn)歸。通常采用主動誘導(dǎo)法制備EAE模型,將抗原與佐劑的混合乳劑直接注射至動物體內(nèi),經(jīng)過一定時間的潛伏期,誘導(dǎo)EAE的產(chǎn)生??乖⑸洳课坏牟煌?,可影響EAE的發(fā)生率、潛伏期、死亡率及復(fù)發(fā)率。常用的注射部位有腳墊、頸部及背部(皮下、皮內(nèi)、肌肉)、腹腔和尾靜脈等多種,其中以皮下多點(diǎn)注射及腳墊注射的發(fā)病率最高,而頸部注射則有較高的復(fù)發(fā)率。 因多次注射易引發(fā)免疫耐受,現(xiàn)在多采用單次注射抗原法。EAE的被動轉(zhuǎn)移實驗是研究其發(fā)病機(jī)制的最直接證據(jù),也是研究EAE的治療及預(yù)防措施的良好模型。

操作流程:

小鼠品系:雌性C57BL/6 小鼠

周齡:6-8周

0天:等體積混合MOG35-55(200ug)和佐劑(CFA,0.5mg)配成乳劑 ,皮下注射100ul/只。

3天:腹腔注射200ng 無菌PBS溶解的百日咳毒素,100ul/只。

典型的EAE發(fā)病時間為免疫后9-14天,免疫后3-5天為高峰期,隨后逐漸恢復(fù)。高峰期持續(xù)1-3天。有25%概率的小鼠在免疫恢復(fù)后,疾病復(fù)發(fā),嚴(yán)重程度增加,通常發(fā)生在免疫后的20-27天。小鼠通常觀察4周左右,在此期間,小鼠將保持慢性癱瘓。

此方案源于文獻(xiàn)(PMID: 20811645),具體的免疫劑量我們建議客戶根據(jù)您的實驗需求制定和優(yōu)化實驗方案。以上方案僅供參考。

EAE的神經(jīng)癥狀通常根據(jù)Kono等提出的標(biāo)準(zhǔn)分為5級。0級:無任何臨床癥狀;1級:動物尾巴無力,2級:尾部無力+肢體無力,3級:肢體輕度麻痹,4級:肢體嚴(yán)重麻痹,被動翻身后不能復(fù)原;5級:瀕死狀態(tài)或死亡。

應(yīng)用文獻(xiàn):

1.Shibamura-Fujiogi, etal.Cathepsin L regulates pathogenic CD4 T cells in experimental autoimmune encephalomyelitis.April 1, 2021,International Immunopharmacology.

2.Shen, PX,etal.Urolithin A ameliorates experimental autoimmune encephalomyelitis by targeting aryl hydrocarbon receptor.January 30, 2021,Ebiomedicine

3.Takeshita,etal.IL-6 blockade suppresses the blood-brain barrier disorder, leading to prevention of onset of NMOSD.January 28, 2021,Biorxiv.

4.Wei, L,etal.Arctigenin Exerts Neuroprotective Effect By Ameliorating Cortical Activities in Experimental Autoimmune Encephalomyelitis in Vivo.January 25, 2021,Research Square.

5.Kim, TW,etal.Bilirubin nanomedicine ameliorates the progression of experimental autoimmune encephalomyelitis by modulating dendritic cells.January 12, 2021,Journal Of The Controlled Release.

6.Yang, R,etal.Diffusion Basis Spectrum Imaging Measures Anti-Inflammatory and Neuroprotective Effects of Fingolimod on Murine Optic Neuritis.January 9, 2021,Research Square.

7.Mimouna, S,etal.Transcription cofactor GRIP1 differentially affects myeloid cell-driven neuroinflammation and response to IFN-β therapy.January 4, 2021,The Journal Of Experimental Medicine.

8.Li, PY.PEGylation enables subcutaneously administered nanoparticles to induce antigen-specific immune tolerance.January 12, 2021,Journal Of Controlled Release.

9.Aqel, SI,etal.A STAT3 inhibitor ameliorates CNS autoimmunity by restoring Teff:Treg Balance.January 7, 2021,JCI Insight.

10.Chaudhary, P,etal.Thyroid hormone and thyromimetics inhibit myelin and axonal degeneration and oligodendrocyte loss in EAE.December 27, 2020,Journal Of Neuroimmunology

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