Quan N, Mhlanga J D, Whiteside M B, McCoy A N, Kristensson K, Herkenham M
Section on Functional Neuroanatomy, National Institute of Mental Health, Bethesda, Maryland 20892-4070, USA.
J Comp Neurol. 1999 Nov 8;414(1):114-30. doi: 10.1002/(sici)1096-9861(19991108)414:1<114::aid-cne9>3.0.co;2-g.
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 parasite Trypanosoma brucei. Several weeks after infection, in situ hybridization histochemistry showed a pattern of chronic overexpression of the mRNAs for proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha in the brains of the animals. Similar spatiotemporal inductions of mRNAs for inhibitory factor kappaBalpha and interleukin-1beta 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-gamma, 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.
转基因动物大脑中促炎细胞因子的过度产生会导致脑部病变。为了研究成年发病、病理生理诱导的脑内细胞因子表达的动物大脑中脑内细胞因子与病变之间的关系，我们对感染了布氏锥虫寄生虫的大鼠进行了研究。感染几周后，原位杂交组织化学显示，这些动物大脑中促炎细胞因子白细胞介素-1β和肿瘤坏死因子-α的mRNA呈慢性过表达模式。发现并定量了抑制因子κBα和白细胞介素-1β转化酶mRNA的类似时空诱导情况。诱导型一氧化氮合酶和白细胞介素-1受体拮抗剂的mRNA高度定位于脉络丛，脉络丛显示出与寄生虫存在相关的结构异常证据。白细胞介素-6、干扰素-γ和诱导型环氧化酶的mRNA显示出受限的诱导模式。另一组动物进行了变性诱导银染色、TdT介导的dUTP-地高辛配基缺口末端标记（TUNEL）染色、胶质纤维酸性蛋白（GFAP）免疫组织化学及其他几种组织学标记检测。在与细胞因子mRNA模式和脑脊液扩散途径在空间上相关的模式中，发现了散在小细胞的凋亡和某些神经纤维的变性。此外，还发现了明显的、细胞构筑学上定义的、可能为星形胶质细胞的变性非神经元细胞簇。结果揭示了在这个自然疾病模型中，大脑中潜在细胞毒性细胞因子的慢性过表达和选择性组织病理学模式。《比较神经学杂志》414:114 - 130, 1999年。1999年由威利 - 利斯公司出版。
