Neuronal IL-4Rα modulates neuronal apoptosis and cell viability during the acute phases of cerebral ischemia

The FEBS Journal
Han Kyu LeeDouglas A Marchuk

Abstract

Ischemic stroke caused by an embolus or local thrombosis results in neural tissue damage (an infarct) in the territory of the occluded cerebral artery. Decades of studies have increased our understanding of the molecular events during cerebral infarction; however, translation of these discoveries to druggable targets for ischemic stroke treatment has been largely disappointing. Interleukin-4 (IL-4) is a multifunctional cytokine that exerts its cellular activities via the interleukin-4 receptor α (IL-4Rα). This cytokine receptor complex is associated with diverse immune and inflammatory responses. Recent studies have suggested a role of the cytokine IL-4 in long-term ischemic stroke recovery, involving immune cell activity. In contrast, the role of the receptor, IL-4Rα especially in the acute phase of infarction is unclear. In this study, we determined that IL-4Rα is expressed on neurons and that during the early phases of cerebral infarction (24 h) levels of this receptor are increased to regulate cellular apoptosis factors through activation of STAT6. In this context, we show a neuroprotective role for IL-4Rα in an in vivo surgical model of cerebral ischemia and in ex vivo brain slice explants, using both genetic knockout of t...Continue Reading

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Citations

Oct 3, 2018·Journal of Molecular Neuroscience : MN·Lu-Yao AoYun-Man Li
Feb 9, 2021·Frontiers in Physiology·Sylvain GiroudKenneth B Storey
Aug 20, 2021·Frontiers in Neuroscience·Han Kyu LeeDouglas A Marchuk
Aug 31, 2021·Cellular and Molecular Neurobiology·Bhakta Prasad Gaire

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Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

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