title: Role of toll-like receptor 2 in ischemic demyelination and oligodendrocyte death.
abstract: White matter is frequently involved in ischemic stroke, and progressive ischemic white matter injuries are associated with various neurologic dysfunctions in the elderly population. Demyelination and oligodendrocyte (OL) loss are prominent features of ischemic white matter injury. Endothelin-1 injection into the internal capsule resulted in a localized demyelinating lesion in mice, where loss of OL lineage cells and inflammatory cell infiltration were observed accompanied by upregulation of toll-like receptor 2 (TLR2). Intriguingly, the extent of demyelinating pathology was markedly larger in TLR2 deficient mice than that of wild-type (WT) mice. TLR2 deficient mice showed enhanced OL death and decreased phosphorylation of ERK1/2 compared with WT animals. Cultured OLs from TLR2 deficient mice were more vulnerable to oxygen-glucose deprivation than WT OLs. Applying TLR2 agonists Pam3CSK4 or Zymosan after oxygen-glucose deprivation substantially rescued WT OL death with augmentation of ERK1/2 phosphorylation. Treatment with Pam3CSK4 also reduced the extent of endothelin-1 induced ischemic demyelination in vivo. Our data indicate TLR2 may provide endogenous protective effects on ischemic demyelination and OL degeneration.
authors.affiliation: Department of Brain Science, Ajou University School of Medicine, Suwon, Korea; Department of Neurology, Ajou University School of Medicine, Suwon, Korea; Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Korea.
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Brain Science, Ajou University School of Medicine, Suwon, Korea; Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Korea.
authors.forename: Yuexian
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Brain Science, Ajou University School of Medicine, Suwon, Korea; Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Korea.
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Kang
authors.affiliation: Department of Pathology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Jang-Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Neuroscience and Physiology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea.
authors.forename: Sung Joong
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Brain Science, Ajou University School of Medicine, Suwon, Korea; Department of Neurology, Ajou University School of Medicine, Suwon, Korea; Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Korea. Electronic address: kimbg@ajou.ac.kr.
authors.forename: Byung G
authors.initials: BG
authors.lastname: Kim
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D019332:Endothelin-1; D056784:Leukoencephalopathies / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D055666:Lipopeptides / Q000494:pharmacology / Q000627:therapeutic use; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009836:Oligodendroglia / Q000473:pathology*; D010766:Phosphorylation / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D019332:Endothelin-1; D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2
keywords: Oligodendrocyte; Stroke; Toll-like receptor 2; White matter