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.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Choi JY,Cui Y,Kang YM,Kim JH,Lee SJ,Kim BG

doi

10.1016/j.neurobiolaging.2014.01.146

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

1643-53

issue

7

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(14)00168-7

journal_volume

35

pub_type

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