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Chronic overexpression of proinflammatory cytokines and histopathology in the brains of rats infected with Trypanosoma brucei
Author(s) -
Quan Ning,
Mhlanga Jama D.M.,
Whiteside Michael B.,
McCoy Allison N.,
Kristensson Krister,
Herkenham Miles
Publication year - 1999
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/(sici)1096-9861(19991108)414:1<114::aid-cne9>3.0.co;2-g
Subject(s) - proinflammatory cytokine , biology , pathology , microglia , interleukin , in situ hybridization , glial fibrillary acidic protein , cytokine , immunohistochemistry , inflammation , immunology , messenger rna , medicine , biochemistry , gene
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‐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.