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Publication : Role of toll-like receptor 2 in ischemic demyelination and oligodendrocyte death.

First Author  Choi JY Year  2014
Journal  Neurobiol Aging Volume  35
Issue  7 Pages  1643-53
PubMed ID  24589120 Mgi Jnum  J:213810
Mgi Id  MGI:5586622 Doi  10.1016/j.neurobiolaging.2014.01.146
Citation  Choi JY, et al. (2014) Role of toll-like receptor 2 in ischemic demyelination and oligodendrocyte death. Neurobiol Aging 35(7):1643-53
abstractText  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.
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