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Leukemia inhibitor factor promotes functional recovery and oligodendrocyte survival in rat models of focal ischemia
Author(s) -
Rowe Derrick D.,
Collier Lisa A.,
Seifert Hilary A.,
Chapman Cortney B.,
Leonardo Christopher C.,
Willing Alison E.,
Pennypacker Keith R.
Publication year - 2014
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12675
Subject(s) - leukemia inhibitory factor , pharmacology , superoxide dismutase , oligodendrocyte , oxidative stress , neuroprotection , protein kinase b , ischemia , neurotrophic factors , biology , signal transduction , immunology , microbiology and biotechnology , cytokine , medicine , endocrinology , biochemistry , central nervous system , interleukin 6 , myelin , receptor
Human umbilical cord blood ( HUCB ) cells have shown efficacy in rodent models of focal ischemia and in vitro systems that recapitulate stroke conditions. One potential mechanism of protection is through secretion of soluble factors that protect neurons and oligodendrocytes ( OL s) from oxidative stress. To overcome practical issues with cellular therapies, identification of soluble factors released by HUCB and other stem cells may pave the way for treatment modalities that are safer for a larger percentage of stroke patients. Among these soluble factors is leukemia inhibitory factor ( LIF ), a cytokine that exerts pleiotropic effects on cell survival. Here, data show that LIF effectively reduced infarct volume, reduced white matter injury and improved functional outcomes when administered to rats following permanent middle cerebral artery occlusion. To further explore downstream signaling, primary oligodendrocyte cultures were exposed to oxygen–glucose deprivation to mimic stroke conditions. LIF significantly reduced lactate dehydrogenase release from OL s, reduced superoxide dismutase activity and induced peroxiredoxin 4 ( P rdx4) transcript. Additionally, the protective and antioxidant capacity of LIF was negated by both A kt inhibition and co‐incubation with P rdx4‐neutralising antibodies, establishing a role for the A kt signaling pathway and P rdx4‐mediated antioxidation in LIF protection.