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TLR2-induced astrocyte MMP9 activation compromises the blood brain barrier and exacerbates intracerebral hemorrhage in animal models

Cited 29 time in Web of Science Cited 27 time in Scopus
Authors
Min, Hyunjung; Hong, Jinpyo; Cho, Ik-Hyun; Jang, Yong Ho; Lee, Hyunkyoung; Kim, Dongwoon; Yu, Seong-Woon; Lee, Soojin; Lee, Sung Joong
Issue Date
2015-04-10
Publisher
BioMed Central
Citation
Molecular Brain. 2015 Apr 10;8(1):23
Keywords
Toll-like receptorStrokeNeuroinflammationNeutrophilMatrix metalloproteinase-9
Abstract
Background
The innate immune response plays an important role in the pathogenesis of intracerebral hemorrhage (ICH). Recent studies have shown that Toll-like receptor 2 (TLR2) is involved in the innate immune response in various neurological diseases, yet neither its role in ICH nor the mechanisms by which it functions have yet been elucidated. We examined these in this study using a collagenase-induced mouse ICH model with TLR2 knock-out (KO) mice.

Results
TLR2 expression was upregulated in the ipsilateral hemorrhagic tissues of the collagenase-injected mice. Brain injury volume and neurological deficits following ICH were reduced in TLR2 KO mice compared to wild-type (WT) control mice. Heterologous blood-transfer experiments show that TLR2 signaling in brain-resident cells, but not leukocytes, contributes to the injury. In our study to elucidate underlying mechanisms, we found that damage to blood–brain barrier (BBB) integrity following ICH was attenuated in TLR2 KO mice compared to WT mice, which may be due to reduced matrix metalloproteinase-9 (MMP9) activation in astrocytes. The reduced BBB damage accompanies decreased neutrophil infiltration and proinflammatory gene expression in the injured brain parenchyma, which may account for the attenuated brain damage in TLR2 KO mice after ICH.

Conclusions
TLR2 plays a detrimental role in ICH-induced brain damage by activating MMP9 in astrocytes, compromising BBB, and enhancing neutrophils infiltration and proinflammatory gene expression.
Language
English
URI
http://hdl.handle.net/10371/109819
DOI
https://doi.org/10.1186/s13041-015-0116-z
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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