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Increase of tumor necrosis factor‐α in the blood induces early activation of matrix metalloproteinase‐9 in the brain
Author(s) -
Tsuge Mitsuru,
Yasui Kozo,
Ichiyawa Takashi,
Saito Yukie,
Nagaoka Yoshiharu,
Yashiro Masato,
Yamashita Nobuko,
Morishima Tsuneo
Publication year - 2010
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2010.00226.x
Subject(s) - blood–brain barrier , cerebrospinal fluid , encephalopathy , tumor necrosis factor alpha , pathogenesis , matrix metalloproteinase , cytokine , sepsis , vascular permeability , medicine , endocrinology , neuroinflammation , inflammation , biology , pathology , immunology , central nervous system
Increases of cytokine in the blood play important roles in the pathogenesis of influenza‐associated encephalopathy. TNF‐α was administered intravenously to wild‐type mice, after which blood, CSF and brain tissue were obtained, and changes in BBB permeability, the amounts of MMP‐9 and TIMP‐1, and the localization of activated MMP were assessed. There was a significant increase in BBB permeability after 6 and 12 hr. MMP‐9 was increased after 3 hr in the brain and cerebrospinal fluid, which was earlier than in the serum. TIMP‐1 protein in the brain increased significantly after MMP‐9 had increased. Activation of MMP‐9 was observed in neurons in the cerebral cortex and hippocampus, and in vascular endothelial cells. These findings suggest that an increase in blood TNF‐α promotes activation of MMP‐9 in the brain, and may also induce an increase in permeability of the BBB. Early activation of MMP‐9 in the brain may contribute to an early onset of neurological disorders and brain edema prior to multiple organ failure in those inflammatory diseases associated with highly increased concentrations of TNF‐α in the blood, such as sepsis, burns, trauma and influenza‐associated encephalopathy.