Abstract
Microglial cells are the first line immune cells that initiate inflammatory responses following cerebral ischemia/reperfusion(I/R) injury. Microglial cells are also associated with a novel subtype of pro-inflammatory programmed cell death known as pyroptosis. Research has been directed at developing treatments that modulate inflammatory responses and protect against cell death caused by cerebral I/R. Key among such treatments include mesenchymal stem cell (MSC) therapy. A unique type of MSC termed olfactory mucosa mesenchymal stem cell (OM-MSC) confers neuroprotection by promoting the secretion of paracrine factors, and neuroprotection. This study investigated whether hypoxic OM-MSCs could inhibit microglial cell death upon I/R insult in vitro. A traditional oxygen-glucose deprivation/reperfusion (OGD/R) model, analogous to I/R, was established. Results showed that OGD/R induced apoptosis and pyroptosis in microglial cells while hypoxia in OM-MSCs significantly attenuated these effects. Moreover, the effects of OM-MSCs were mediated by Hypoxia-inducible factor 1-alpha (HIF-1α). Taken together, these findings reveal that hypoxia-preconditioned OM-MSC inhibits pyroptotic and apoptotic death of microglial cell in response to cerebral ischemia/reperfusion insult by activating HIF-1α in vitro.
Highlights
Among central nervous system (CNS) diseases, cerebral ischemic stroke is the most common cause of death and disability [1]
HIF-1α, a protein was sensitive to oxidative concentration, has been reported to regulate responses to hypoxia [23]. To date, it is not known whether co-culturing olfactory mucosa (OM)-mesenchymal stem cell (MSC) with microglia has a protective effect against either pyroptotic or apoptotic cell death during cerebral I/R injury
These results indicated that oxygen-glucose deprivation/reperfusion (OGD/R) induced apoptotic cell death in BV2 microglial cells
Summary
Among central nervous system (CNS) diseases, cerebral ischemic stroke is the most common cause of death and disability [1]. This condition has been successfully treated with tissue plasminogen activator (tPA) therapy. The reperfusion process may result in serious brain tissue damage [2], and has been an intractable challenge in stroke treatment It is, crucial to elucidate the latent mechanisms of cerebral I/R injury. Numerous studies have demonstrated that pyroptosis is extensively involved in CNS disorders [6,7,8] It shares similar features with apoptotic cell death such as DNA fragmentation. Information regarding microglia and their contribution to pyroptosis during cerebral I/R is still insufficient
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