Chronic overexpression of proinflammatory cytokines and histopathology in the brains of rats infected with Trypanosoma brucei.
Chronic overexpression of proinflammatory cytokines and histopathology in the brains of rats infected with Trypanosoma brucei.
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感染布氏锥虫的大鼠大脑中促炎细胞因子的慢性过度表达和组织病理学。
DOI：
10.1002/(sici)1096-9861(19991108)414:1
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Herkenham,M
中科院分区：
文献类型：
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作者：
Quan,N;Mhlanga,JD;Whiteside,MB;McCoy,AN;Kristensson,K;Herkenham,M
在转基因动物的大脑中，促炎细胞因子的过量产生会导致脑部病理。为了研究脑细胞因子与成年发病、病理生理诱导的脑细胞因子表达的关系，我们研究了感染布鲁氏斑虫的大鼠。感染几周后，原位杂交组织化学显示动物大脑中促炎细胞因子白介素- 1β和肿瘤坏死因子- α mrna的慢性过表达模式。抑制因子κBα和白细胞介素- 1β转换酶的mrna在时空上也有相似的诱导作用。诱导型一氧化氮合酶和白细胞介素- 1受体拮抗剂的mrna高度定位于脉络膜丛，这表明与寄生虫存在相关的结构异常的证据。白细胞介素- 6、干扰素- γ和诱导型环加氧酶的mrna显示出有限的诱导模式。另一组动物进行变性诱导的银染色、TdT介导的dUTP -地高igenin缺口末端标记（TUNEL）染色、胶质纤维酸性蛋白（GFAP）免疫组织化学和其他一些组织学标记。分散的小细胞凋亡和某些神经纤维变性的模式与细胞因子mRNA模式和脑脊液扩散途径在空间上相关。此外，还发现了明显的细胞结构明确的变性非神经元细胞簇，可能是星形胶质细胞。结果揭示了大脑中潜在细胞毒性细胞因子的慢性过度表达和这种自然疾病模型的选择性组织病理学模式。[j]中华神经科杂志，1999。出版于1999年Wiley - Liss， Inc。
Overproduction of proinflammatory cytokines in the brains of transgenic animals causes brain pathology. To investigate the relationship between brain cytokines and pathology in the brains of animals with adult‐onset, pathophysiologically induced brain cytokine expression, we studied rats infected with the parasiteTrypanosoma brucei. Several weeks after infection, in situ hybridization histochemistry showed a pattern of chronic overexpression of the mRNAs for proinflammatory cytokines interleukin‐1β and tumor necrosis factor‐α in the brains of the animals. Similar spatiotemporal inductions of mRNAs for inhibitory factor κBα and interleukin‐1β converting enzyme were found and quantified. The mRNAs for inducible nitric oxide synthase and interleukin‐1 receptor antagonist were highly localized to the choroid plexus, which showed evidence of structural abnormalities associated with the parasites' presence there. The mRNAs for interleukin‐6, interferon‐γ, and inducible cyclooxygenase showed restricted induction patterns. Another set of animals was processed for degeneration‐induced silver staining, TdT‐mediated dUTP‐digoxigenin nick end‐labeling (TUNEL) staining, glial fibrillary acidic protein (GFAP) immunohistochemistry, and several other histological markers. Apoptosis of scattered small cells and degeneration of certain nerve fibers was found in patterns spatially related to the cytokine mRNA patterns and to cerebrospinal fluid diffusion pathways. Furthermore, striking cytoarchitectonically defined clusters of degenerating non‐neuronal cells, probably astrocytes, were found. The results reveal chronic overexpression of potentially cytotoxic cytokines in the brain and selective histopathology patterns in this natural disease model. J. Comp. Neurol. 414:114–130, 1999. Published 1999 Wiley‐Liss, Inc.