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Evidence for Multiple Pathologic and Protective Mechanisms of Murine Cerebral Malaria

机译:鼠脑疟疾的多种病理和保护机制的证据

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Murine cerebral malaria (CM) induced by Plasmodium berghei ANKA kills susceptible mice within 24 to 48 h of onset of symptoms and is characterized by the production of inflammatory cytokines in the brain. C57BL/6J mice are sensitive to lethal CM, while A/J mice are resistant. These strains of mice were immunized with an adjuvant vaccine of killed whole-blood-stage parasites. The immunization protected C57BL/6 mice from lethal CM following virulent challenge. The same immunization increased the incidence of lethal CM in A/J mice challenged similarly. Histopathologic examination of the brains of mice from these studies revealed two distinct types of lesions. Type I CM is acute in onset; usually lethal; and characterized by widespread microglial activation, endothelial cell damage, and microvascular disruption in the brain. Type II CM is characterized by intense, but focal, mononuclear cell inflammation without endothelial cell damage or microvascular destruction. Animals with type II lesions were clinically normal and protected from type I lesions. Available clinical, epidemiological, and biochemical evidence suggests that type I and type II lesions might exist in human CM as well.
机译:伯氏疟原虫ANKA诱发的鼠类脑疟疾在症状发作后24至48小时内杀死易感小鼠,其特征是在大脑中产生炎性细胞因子。 C57BL / 6J小鼠对致命的CM敏感,而A / J小鼠具有抗性。这些小鼠品系用杀死的全血期寄生虫的佐剂疫苗免疫。在强力攻击后,免疫保护了C57BL / 6小鼠免受致命CM的侵害。相同的免疫接种增加了以类似方式攻击的A / J小鼠中致命性CM的发生率。这些研究对老鼠的大脑进行了组织病理学检查,发现了两种不同类型的病变。 I型CM起病急性。通常致命;其特点是广泛的小胶质细胞激活,内皮细胞损伤和大脑中的微血管破坏。 II型CM的特征是剧烈但局灶性单核细胞炎症,而没有内皮细胞损伤或微血管破坏。具有II型病变的动物在临床上是正常的,并受到I型病变的保护。现有的临床,流行病学和生化证据表明,人CM中也可能存在I型和II型病变。

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