【摘要】：由于成體大腦自我修復能力有限,在經(jīng)歷創(chuàng)傷或者疾病之后無法通過自身來彌補損傷神經(jīng)元的丟失,因此大量的研究試圖通過移植外源的胚胎腦組織塊來替代損傷的腦區(qū),進而促進相應的大腦損傷功能的恢復。這些研究結果表明移植的神經(jīng)元不僅能夠重建受體大腦受損的神經(jīng)環(huán)路并且能促進皮層功能的恢復。一個成功的移植不只要重建受損的神經(jīng)元,還要重建其他的例如膠質(zhì)細胞等細胞群體。這其中就包括影響移植物存活和突觸連接、重塑的關鍵細胞:小膠質(zhì)細胞。作為中樞神經(jīng)系統(tǒng)內(nèi)具有免疫活性的一類細胞,小膠質(zhì)細胞在不同生理病理條件下的大腦中具有多種多樣的功能。此外在不同的病理條件下的成體大腦內(nèi),激活態(tài)的小膠質(zhì)細胞可以有不同的來源。雖然在正常和病理條件下的大腦中,小膠質(zhì)細胞的動態(tài)變化和來源情況已經(jīng)被描述的很清楚,但是在移植的胚胎腦組織塊中其形態(tài)和數(shù)量變化的情況還不是很清楚。本論文利用小膠質(zhì)細胞特異性表達綠色熒光蛋白的轉基因小鼠和雙光子活體成像技術來研究胚胎腦組織塊移植模型中移植小膠質(zhì)細胞的存活情況和受體來源的小膠質(zhì)細胞的侵入、增殖和分化的過程。同時,結合異種共生血液嵌合模型研究移植塊內(nèi)受體小膠質(zhì)細胞的來源和命運。我們的結果表明移植的神經(jīng)元能夠成功在受體大腦內(nèi)存活和分化。和移植的神經(jīng)元的命運不同,胚胎腦組織移植塊內(nèi)的小膠質(zhì)細胞卻在移植到受體大腦內(nèi)后迅速的消失。相反,移植區(qū)域里分布的小膠質(zhì)細胞被證實是來源于侵入的受體細胞。同時,侵入的小膠質(zhì)細胞在經(jīng)歷增殖和劇烈的形態(tài)學變化后,最終慢慢的分化成為靜息態(tài)的狀態(tài)。血液嵌合模型則表明這些侵入的受體來源的小膠質(zhì)細胞主要來源于大腦實質(zhì)。綜上,我們的結果揭示了受體大腦實質(zhì)來源的小膠質(zhì)細胞侵入到移植區(qū)域后恢復該區(qū)域的小膠質(zhì)細胞群落的過程,該結果揭示了胚胎移植塊內(nèi)的小膠質(zhì)細胞的來源和分化的問題,為該移植方法在臨床上的應用提供了一定的理論支持。
[Abstract]:Due to the limited ability of the adult brain to repair itself, it is not possible to compensate for the loss of injured neurons by itself after experiencing trauma or disease. Therefore, a large number of studies have attempted to replace the damaged brain regions by transplanting exogenous embryonic brain tissue blocks. And then promote the recovery of brain injury function. These results suggest that the transplanted neurons can not only reconstruct the injured neural loop of the receptor brain, but also promote the recovery of cortical function. A successful transplant involves not only rebuilding damaged neurons, but also other cell groups, such as glial cells. These include key cells that affect graft survival and synaptic connections, remodeling: microglia. As a class of immune cells in the central nervous system, microglia have a variety of functions in the brain under different physiological and pathological conditions. In addition, activated microglia may come from different sources in the adult brain under different pathological conditions. Although the dynamic changes and origin of microglia in the normal and pathological brain have been described clearly, the morphological and quantitative changes of microglia in the transplanted embryonic brain mass are not very clear. In this paper, the microglia specific expression of green fluorescent protein in transgenic mice and two-photon imaging were used to study the survival of transplanted microglia and the small recipient source in the model of embryonic brain tissue transplantation. The invasion of glial cells, The process of proliferation and differentiation. At the same time, the origin and fate of the receptor microglia in the graft block were studied by using the blood chimerism model of xenosymbiosis. Our results suggest that the transplanted neurons can successfully survive and differentiate in the receptor brain. Unlike the fate of the transplanted neurons, the microglia in the embryonic brain tissue graft rapidly disappeared after being transplanted into the recipient brain. Instead, microglia distributed in the transplant area were confirmed to be derived from invading receptor cells. At the same time, the invasive microglia gradually differentiated into a resting state after experiencing proliferation and severe morphological changes. The blood chimerism model showed that the microglia derived from these invading receptors were mainly derived from the brain parenchyma. In summary, our results reveal the process by which microglia from parenchymal sources of the receptor brain invade into the transplanted region and recover the microglia community in that region. The results reveal the origin and differentiation of microglia in embryo transfer and provide some theoretical support for the clinical application of this method.
【學位授予單位】：蘭州大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R741

【相似文獻】

相關期刊論文 前10條

1 陸華寶,李林;腦巨噬細胞/小膠質(zhì)細胞在中樞神經(jīng)系統(tǒng)疾病或損傷修復中的作用[J];中國康復理論與實踐;2002年03期

2 杜一星,王偉;小膠質(zhì)細胞的活化與調(diào)控[J];國外醫(yī)學(腦血管疾病分冊);2004年08期

3 李小媚;李愛萍;;小膠質(zhì)細胞的發(fā)育和功能[J];解剖學研究;2010年03期

4 楊逢春;顯示小膠質(zhì)細胞方法的改進[J];解剖學研究;2002年02期

5 袁瓊蘭,郭勇,王瓊,鄧莉,高小青,余鴻,古元;小膠質(zhì)細胞培養(yǎng)、分離、純化和鑒定的初步研究[J];瀘州醫(yī)學院學報;2002年05期

6 劉鋒,朱長庚;小膠質(zhì)細胞激活的分子機制[J];解剖科學進展;2003年02期

7 蔣平,彭艷,倪健,向正華,焦炳華;小膠質(zhì)細胞蛋白質(zhì)組三維分離方法的建立[J];第二軍醫(yī)大學學報;2005年06期

8 熊懷林,范光碧,胡興宇;小膠質(zhì)細胞在腦缺血中的作用[J];四川解剖學雜志;2005年02期

9 魏桂榮,張敏,董繼華,梅元武,劉仁剛;構建一種高產(chǎn)量小膠質(zhì)細胞體外純化培養(yǎng)的方法(英文)[J];中國臨床康復;2005年21期

10 趙洋;孫素真;;小膠質(zhì)細胞和癲癇[J];中國神經(jīng)免疫學和神經(jīng)病學雜志;2008年01期

相關會議論文 前10條

1 韓書珍;李雪梅;牛文澤;陳翔;王果;李澤宜;;激光掃描共聚焦顯微鏡觀察大鼠局灶性腦缺血半暗區(qū)內(nèi)小膠質(zhì)細胞的變化及意義[A];第六屆江浙滬兒科學術會議暨兒科學基礎與臨床研究進展學術班論文匯編[C];2009年

2 李捷;劉勇;張蓬勃;肖新莉;呂海俠;李敏杰;康前雁;鄧美英;;大鼠局灶性腦缺血后小膠質(zhì)細胞的來源[A];解剖學雜志——中國解剖學會2002年年會文摘匯編[C];2002年

3 賈思遠;雷露雯;王克萬;王勇;;煙堿型乙酰膽堿受體在離體海馬小膠質(zhì)細胞上的表達與定位[A];廣東省藥學會2009學術年會論文集[C];2010年

4 劉鋒;朱長庚;劉慶瑩;;小膠質(zhì)細胞的激活及其在致癇過程中的作用機制[A];解剖學雜志——中國解剖學會2002年年會文摘匯編[C];2002年

5 趙天智;;血清白蛋白刺激小膠質(zhì)細胞前炎癥細胞因子表達的作用研究[A];中華醫(yī)學會神經(jīng)外科學分會第九次學術會議論文匯編[C];2010年

6 趙敏;袁云;趙培園;李t，

本文編號：2185849