title: TLR2-induced astrocyte MMP9 activation compromises the blood brain barrier and exacerbates intracerebral hemorrhage in animal models.
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.
authors: Department of Neuroscience and Physiology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 110-749, South Korea. showgi84@hotmail.com.
authors: Hyunjung
authors: H
authors: Min
authors: Department of Neuroscience and Physiology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 110-749, South Korea. biojp@gmail.com.
authors: Jinpyo
authors: J
authors: Hong
authors: Department of Convergence Medical Science, College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, South Korea. ihcho@khu.ac.kr.
authors: Ik-Hyun
authors: IH
authors: Cho
authors: Department of Neuroscience and Physiology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 110-749, South Korea. powerups@naver.com.
authors: Yong Ho
authors: YH
authors: Jang
authors: Department of Neuroscience and Physiology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 110-749, South Korea. yolong-97@hanmail.net.
authors: Hyunkyoung
authors: H
authors: Lee
authors: Department of Anatomy, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon, 305-764, South Korea. visnu528@cnu.ac.kr.
authors: Dongwoon
authors: D
authors: Kim
authors: Department of Brain Science, Daegu Gyeongbuk Institute of Science and Technology, Daegu, 711-873, Republic of Korea. yusw@dgist.ac.kr.
authors: Seong-Woon
authors: SW
authors: Yu
authors: Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon, 305-764, South Korea. leesoojin@cnu.ac.kr.
authors: Soojin
authors: S
authors: Lee
authors: Department of Neuroscience and Physiology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 110-749, South Korea. sjlee87@snu.ac.kr.
authors: Sung Joong
authors: SJ
authors: Lee
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000201:enzymology* / Q000473:pathology; D001812:Blood-Brain Barrier / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000201:enzymology* / Q000473:pathology*; D018925:Chemokines / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004789:Enzyme Activation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000378:metabolism*
chemical_list: D018925:Chemokines; D051195:Toll-Like Receptor 2; D018799:Intercellular Adhesion Molecule-1; D017364:Collagenases; D020780:Matrix Metalloproteinase 9