Medana I M, Hunt N H, Chan-Ling T
Department of Pathology, University of Sydney, New South Wales, Australia.
Glia. 1997 Feb;19(2):91-103. doi: 10.1002/(sici)1098-1136(199702)19:2<91::aid-glia1>3.0.co;2-c.
Microglia are pluripotent members of the macrophage/monocyte lineage that can respond in several ways to pathological changes in the central nervous system. To determine their role in the pathogenesis of fatal murine cerebral malaria (FMCM) we have conducted a detailed study of the changes in morphology and distribution of retinal microglia during the progression of the disease. Adult CBA/T6 mice were inoculated with Plasmodium berghei ANKA. These mice died 7 days post inoculation (p.i.) with the parasite while exhibiting cerebral symptoms, increased permeability of the blood-brain barrier, and monocyte adherence to the vascular endothelium. Mice were injected i.v. with Monastral blue 2 h prior to sacrifice to identify "activated" monocytes, and their isolated retinae were incubated with the Griffonia simplicifolia (GS) lectin or reacted for the nucleoside diphosphatase enzyme to visualize microglia and the vasculature. Changes in microglial morphology were seen within 2-3 days p.i., that is, at least 3 days prior to the onset of cerebral symptoms and 4 days before death. Morphological changes included retraction of ramified processes, soma enlargement, an increasingly amoeboid appearance, and vacuolation. There was also increased staining intensity and redistribution of "activated" microglia toward retinal vessels, but no increase in density of NDPase-positive cells. The GS lectin only labeled a small population of microglia in the uninfected adult mouse retina. However, there was a striking increase in the focal density of GS-positive microglia during the progression of the disease. Extravasation of monocytes also was observed prior to the onset of cerebral symptoms. These results provide the first evidence that microglial activation is a critical component of the pathological process during FMCM.
小胶质细胞是巨噬细胞/单核细胞谱系中的多能成员，能够以多种方式对中枢神经系统的病理变化做出反应。为了确定它们在致命性小鼠脑型疟疾（FMCM）发病机制中的作用，我们对疾病进展过程中视网膜小胶质细胞的形态和分布变化进行了详细研究。成年CBA/T6小鼠接种伯氏疟原虫ANKA。这些小鼠在接种寄生虫后7天死亡，同时出现脑部症状、血脑屏障通透性增加以及单核细胞黏附于血管内皮。在处死前2小时经静脉注射给小鼠注射台盼蓝以识别“活化”的单核细胞，分离出的视网膜与西非相思豆（GS）凝集素一起孵育，或进行核苷二磷酸酶反应以观察小胶质细胞和脉管系统。在接种后2 - 3天内观察到小胶质细胞形态的变化，即至少在脑部症状出现前3天和死亡前4天。形态学变化包括分支状突起的回缩、胞体增大、越来越呈阿米巴样外观以及空泡化。“活化”的小胶质细胞向视网膜血管的染色强度也增加且重新分布，但NDP酶阳性细胞的密度没有增加。GS凝集素仅标记未感染成年小鼠视网膜中的一小部分小胶质细胞。然而，在疾病进展过程中，GS阳性小胶质细胞的局灶密度显著增加。在脑部症状出现之前也观察到了单核细胞的渗出。这些结果提供了首个证据，表明小胶质细胞活化是FMCM病理过程的关键组成部分。
