Nakashima H, Kawamura K, Date I
Department of Neurological Surgery, Okayama University Medical School, Japan.
Brain Res. 1988 Dec 20;475(2):232-43. doi: 10.1016/0006-8993(88)90611-7.
Pieces of brainstem tissue from mouse embryos were transplanted into the cerebellar vermis of 49 adult rats, which had or which had not been treated with Cyclosporin A (10 mg/kg/day). With no treatment of immunosuppressants survival rates of xenografts were low. However, when Cyclosporin A was administered, the rates increased from 40% (4/10) to 67% (8/12) 2 weeks after grafting and from 25% (3/12) to 60% (9/15) 4 weeks after grafting, although immunological reactions of varying severities were noted in all of the surviving grafts. The present immunocytochemical study elucidated the composition of cell infiltrations frequently seen in the grafts. The results showed that a large number of cytotoxic/suppressor T lymphocytes appeared, while the numbers of helper/inducer T lymphocytes were relatively small. In addition, increased staining of astrocytes and microglia was observed in areas of cell infiltration. These activated cells might play a certain role in the process of graft rejection in the brain. Formation of the blood-brain barrier in the xenografts was examined by means of peroxidase cytochemistry and immunohistochemistry. In brains containing surviving grafts limited leakage of peroxidase, following its injection into the host systemic circulation 30-75 min prior to sacrifice, was detectable at the graft-host interface and at the operation scar near the pial surface. In brains containing rejected grafts extensive extravasation of peroxidase was detected. The severity of the immunological reaction was correlated with the intensity of the rupture in the blood-brain barrier. The findings suggested that the immunological reaction contributed to the transendothelial permeability changes in the vessels of brains containing rejected grafts.
将小鼠胚胎的脑干组织块移植到49只成年大鼠的小脑蚓部，这些大鼠接受或未接受环孢素A（10毫克/千克/天）治疗。未使用免疫抑制剂时，异种移植物的存活率很低。然而，给予环孢素A后，移植后2周存活率从40%（4/10）提高到67%（8/12），移植后4周从25%（3/12）提高到60%（9/15），尽管在所有存活的移植物中都观察到了不同程度的免疫反应。目前的免疫细胞化学研究阐明了移植物中常见的细胞浸润成分。结果显示，出现了大量细胞毒性/抑制性T淋巴细胞，而辅助/诱导性T淋巴细胞数量相对较少。此外，在细胞浸润区域观察到星形胶质细胞和小胶质细胞的染色增加。这些活化细胞可能在脑内移植物排斥过程中发挥一定作用。通过过氧化物酶细胞化学和免疫组织化学方法检测异种移植物中血脑屏障的形成。在含有存活移植物的脑中，在处死前30 - 75分钟将过氧化物酶注入宿主全身循环后，在移植物 - 宿主界面和软脑膜表面附近的手术瘢痕处可检测到有限的过氧化物酶渗漏。在含有排斥移植物的脑中检测到过氧化物酶的广泛外渗。免疫反应的严重程度与血脑屏障破裂的强度相关。这些发现表明，免疫反应导致了含有排斥移植物的脑内血管内皮通透性的变化。
