Abstract
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,
| Original language | English |
|---|---|
| Pages (from-to) | 417-424 |
| Number of pages | 8 |
| Journal | Microbiology and Immunology |
| Volume | 54 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 2010 |
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Keywords
- Blood-brain barrier
- Influenza associated encephalopathy
- Matrix metalloproteinase-9
- Tumor necrosis factor-alpha
ASJC Scopus subject areas
- Immunology
- Microbiology
- Virology
Cite this
Increase of tumor necrosis factor-α in the blood induces early activation of matrix metalloproteinase-9 in the brain. / Tsuge, Mitsuru; Yasui, Kozo; Ichiyawa, Takashi; Saito, Yukie; Nagaoka, Yoshiharu; Yashiro, Masato; Yamashita, Nobuko; Morishima, Tsuneo.
In: Microbiology and Immunology, Vol. 54, No. 7, 07.2010, p. 417-424.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Increase of tumor necrosis factor-α in the blood induces early activation of matrix metalloproteinase-9 in the brain
AU - Tsuge, Mitsuru
AU - Yasui, Kozo
AU - Ichiyawa, Takashi
AU - Saito, Yukie
AU - Nagaoka, Yoshiharu
AU - Yashiro, Masato
AU - Yamashita, Nobuko
AU - Morishima, Tsuneo
PY - 2010/7
Y1 - 2010/7
N2 - 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,
AB - 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,
KW - Blood-brain barrier
KW - Influenza associated encephalopathy
KW - Matrix metalloproteinase-9
KW - Tumor necrosis factor-alpha
UR - http://www.scopus.com/inward/record.url?scp=77954530003&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954530003&partnerID=8YFLogxK
U2 - 10.1111/j.1348-0421.2010.00226.x
DO - 10.1111/j.1348-0421.2010.00226.x
M3 - Article
C2 - 20618688
AN - SCOPUS:77954530003
VL - 54
SP - 417
EP - 424
JO - Microbiology and Immunology
JF - Microbiology and Immunology
SN - 0385-5600
IS - 7
ER -