Astrocytic phagocytosis contributes to demyelination after focal cortical ischemia in mice.

ABSTRACT: Ischemic stroke can cause secondary myelin damage in the white matter distal to the primary injury site. The contribution of astrocytes during secondary demyelination and the underlying mechanisms are unclear. Here, using a mouse of distal middle cerebral artery occlusion, we show that lipocalin-2 (LCN2), enriched in reactive astrocytes, expression increases in nonischemic areas of the corpus callosum upon injury. LCN2-expressing astrocytes acquire a phagocytic phenotype and are able to uptake myelin. Myelin removal is impaired in Lcn2^-/- astrocytes. Inducing re-expression of truncated LCN2(Δ2-20) in astrocytes restores phagocytosis and leads to progressive demyelination in Lcn2^-/- mice. Co-immunoprecipitation experiments show that LCN2 binds to low-density lipoprotei

SUBMITTER: Wan T 

PROVIDER: S-EPMC8894352 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature