Marker O, Nielsen M H, Diemer N H
Acta Neuropathol. 1984;63(3):229-39. doi: 10.1007/BF00685249.
The ultrastructure and the blood-brain-barrier (BBB) permeability were studied in mice suffering from lymphocytic choriomeningitis (LCM). Brains and meninges from mice suffering from LCM virus-induced lymphocytic choriomeningitis were studied by investigating the BBB function and by electron and light microscopy. The cellular exudate in the leptomeninges was located in the subarachnoid space, in arachnoidea and pia, and it was dominated by proliferated pial cells and mononuclear cells, most of which were lymphocytes, while there were only a few neutrophil granulocytes. Many intravascular lymphocytes were seen adhering to as well as penetrating the vessel walls. Many of these lymphocytes were morphologically compatible with T cells. Lymphocytes and larger mononuclear cells were also accumulated in the choroid plexus, and lymphocytes were present in the ventricular system with a tendency to adhere to ependymal epithelial cells. Inspection of the ultrathin sections incubated for horseradish peroxidase (HRP)-activity revealed that the overwhelming part of the peroxidase activity was localized in the extracellular space of the meningeal vessel walls and especially in the abundant intercellular fluid which, like the inflammatory cells, was found in the subarachnoid space in arachnoidea and in pia. In the neuropil, only very small quantities of reaction product were seen intercellularly in the most superficial layers of the cortex. The tight junctions were always intact, but the possibility of a non-demonstrable opening is discussed. Evaluation of the BBB permeability for 2-amino[1-14C]isobutyric acid (AIB) was made by quantitative autoradiography, and it was demonstrated convincingly that AIB concentrations in the subpial and perichorodial tissues were markedly increased in diseased animals as compared to the controls. Our results seem to contradict previous theories on the cause of death resulting from the LCM disease. The findings presented here do not speak in favor of a pronounced brain edema, just as results obtained by us and others do not speak for the possibility of the death being caused by convulsive seizures with subsequent brain anoxia. However, our observations are compatible with the hypothesis that cytotoxic T cells may interact in vivo with virus-infected targets, which are essential for the regulation of the composition of the cerebrospinal fluid. On the other hand, the dysfunction of the BBB demonstrated adds a new element to the pathologic mechanism in a model for the study of virus-induced meningitis.
对患有淋巴细胞性脉络丛脑膜炎（LCM）的小鼠的超微结构和血脑屏障（BBB）通透性进行了研究。通过研究血脑屏障功能以及电子显微镜和光学显微镜，对患有LCM病毒诱导的淋巴细胞性脉络丛脑膜炎的小鼠的脑和脑膜进行了研究。软脑膜中的细胞渗出物位于蛛网膜下腔、蛛网膜和软脑膜中，主要由增生的软膜细胞和单核细胞组成，其中大多数是淋巴细胞，而中性粒细胞很少。可见许多血管内淋巴细胞粘附并穿透血管壁。这些淋巴细胞中的许多在形态上与T细胞相符。淋巴细胞和较大的单核细胞也积聚在脉络丛中，并且淋巴细胞存在于脑室系统中，有粘附于室管膜上皮细胞的趋势。对用辣根过氧化物酶（HRP）活性孵育的超薄切片的检查显示，过氧化物酶活性的绝大部分位于脑膜血管壁的细胞外空间，特别是在丰富的细胞间液中，这种细胞间液与炎症细胞一样，存在于蛛网膜和软脑膜的蛛网膜下腔中。在神经纤维网中，仅在皮质最表层的细胞间看到极少量的反应产物。紧密连接始终完整，但讨论了是否存在无法证明的开放可能性。通过定量放射自显影评估了血脑屏障对2-氨基[1-¹⁴C]异丁酸（AIB）的通透性，令人信服地证明，与对照组相比，患病动物软膜下和脉络丛周围组织中的AIB浓度明显增加。我们的结果似乎与先前关于LCM疾病死亡原因的理论相矛盾。此处呈现的发现并不支持明显的脑水肿，正如我们和其他人获得的结果也不支持惊厥性癫痫发作随后导致脑缺氧而引起死亡的可能性。然而，我们的观察结果与细胞毒性T细胞可能在体内与病毒感染的靶标相互作用的假设相符，这些靶标对于调节脑脊液的成分至关重要。另一方面，所证明的血脑屏障功能障碍为病毒诱导的脑膜炎研究模型中的病理机制增添了一个新元素。
