Thomas L, Aleu F, Bitensky M W, Davidson M, Gesner B
J Exp Med. 1966 Dec 1;124(6):1067-82. doi: 10.1084/jem.124.6.1067.
Rolling disease has been produced and studied in rats and mice, using the exotoxin of the A strain of Mycoplasma neurolyticum. The primary lesion of the brain consists of spongiform degeneration, associated with vesicle formation in the cortex and underlying white matter of the cerebral hemispheres, and in the molecular layer of the cerebellum. The brains of animals surviving 2 days or longer show extensive necrotizing lesions resembling ischemic necrosis, in both cerebral hemispheres. The brains of rats and mice with rolling disease become deeply stained by intraperitoneally injected trypan blue, indicating early disruption of the blood brain barrier. The toxin appears to be a thermolabile protein with a molecular weight exceeding 200,000. It is only active when injected by vein, and causes no disease when injected intracerebrally, intraperitoneally or subcutaneously, suggesting the existence of specific receptors within the vascular bed of the central nervous system. Protection is afforded by rabbit antibody against the toxin, but only when antibody is injected within less than 3 min after intravenous injection of toxin, indicating rapid fixation to receptors in the brain. The toxin is inactivated by incubation for 10 min at 37 degrees C with suspensions of the sedimentable component of normal brain. The inactivating factor in brain sediment is very thermostable, not affected by trypsin, and eliminated by treatment with periodate. Similar inactivation of toxin is demonstrable with water-soluble gangliosides of brain. A theoretical concept to explain the action of the toxin is proposed.
利用溶神经支原体A株的外毒素在大鼠和小鼠中引发并研究了翻滚病。脑部的原发性病变包括海绵状变性,与大脑半球皮质及深层白质以及小脑分子层中的囊泡形成有关。存活2天或更长时间的动物大脑在两个大脑半球均显示出广泛的坏死性病变,类似于缺血性坏死。患有翻滚病的大鼠和小鼠的大脑经腹腔注射台盼蓝后会被深度染色,表明血脑屏障早期遭到破坏。该毒素似乎是一种分子量超过200,000的不耐热蛋白质。它仅在静脉注射时具有活性,脑内、腹腔内或皮下注射时不会引发疾病,这表明中枢神经系统血管床内存在特定受体。兔抗毒素抗体可提供保护作用,但仅在静脉注射毒素后不到3分钟内注射抗体时才有效,这表明毒素能迅速与脑内受体结合。将毒素与正常脑可沉淀成分的悬浮液在37℃孵育10分钟后,毒素会失活。脑沉淀物中的失活因子非常耐热,不受胰蛋白酶影响,经高碘酸盐处理后可被去除。用脑的水溶性神经节苷脂也可证明毒素有类似的失活情况。本文提出了一个解释该毒素作用的理论概念。