Argon neuroprotection in ischemic stroke and its underlying mechanism
Li Bao, Yongxin Liu, Qi Jia, Sihao Chu, Han Jiang, Shuang He
Abstract
Ischemic stroke (IS), primarily caused by cerebrovascular obstruction, results in severe neurological deficits and has emerged as a leading cause of death and disability worldwide. Recently, there has been increasing exploration of the neuroprotective properties of the inert gas argon. Argon has exhibited impressive neuroprotection in many in vivo and ex vivo experiments without signs of adverse effects, coupled with the advantages of being inexpensive and easily available. However, the efficient administration strategy and underlying mechanisms of neuroprotection by argon in IS are still unclear. This review summarizes current research on the neuroprotective effects of argon in IS with the goal to provide effective guidance for argon application and to elucidate the potential mechanisms of argon neuroprotection. Early and appropriate argon administration at as high a concentration as possible offers favorable neuroprotection in IS. Argon inhalation has been shown to provide some long-term protection benefits. Argon provides the anti-oxidative stress, anti-inflammatory and anti-apoptotic cytoprotective effects mainly around Toll-like receptor 2/4 (TLR2/4), mediated by extracellular signal-regulated kinase 1/2 (ERK1/2), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), nuclear factor kappa-B (NF-ĸB) and B-cell leukemia/lymphoma 2 (Bcl-2). Therefore, argon holds significant promise as a novel clinical neuroprotective gas agent for ischemic stroke after further researches to identify the optimal application strategy and elucidate the underlying mechanism. • Early and appropriate argon administration in high concentrations offers favorable neuroprotection before reperfusion following ischemic stroke. • Argon offers cytoprotective effects against oxidative stress, inflammation, and apoptosis mainly via TLR2/4, ERK1/2, Nrf2, NF-ĸB, and Bcl-2. • Argon can inhibit microglia and astrocyte activation and promote microglia polarization to M2 type after ischemic stroke.