Oncostatin M Confers Neuroprotection against Ischemic Stroke

Cell-surface receptors provide potential targets for the translation of bench-side findings into therapeutic strategies; however, this approach for the treatment of stroke is disappointing, at least partially due to an incomplete understanding of the targeted factors. Previous studies of oncostatin M (OSM), a member of the gp130 cytokine family, have been limited, as mouse models alone may not strongly resemble the human condition enough. In addition, the precise function of OSM in the CNS remains unclear. Here, we report that human OSM is neuroprotective in vivo and in vitro by recruiting OSMR beta in the setting of ischemic stroke. Using gain- and loss-of-function approaches, we demonstrated that decreased neuronal OSMR beta expression results in deteriorated stroke outcomes but that OSMR beta overexpression in neurons is cerebroprotective. Moreover, administering recombinant human OSM to mice before the onset of I/R showed that human OSM can be protective in rodent models of ischemic stroke. Mechanistically, OSM/OSMR beta activate the JAK2/STAT3 prosurvival signaling pathway. Collectively, these data support that human OSM may represent a promising drug candidate for stroke treatment.