Abstract
BackgroundThe present study aims to investigate the protective effects of dexmedetomidine (DMED) on hypoxia ischemia injury induced by oxygen and glucose deprivation (OGD) in PC12 and primary neuronal cells.MethodsPC12 cells exposed to OGD was used to establish ischemia model. The OGD-induced cell injury was evaluated by alterations of cell viability, apoptosis and expressions of apoptosis-associated proteins. Oxidative stress and expressions of neurotrophic factors after OGD and DMED treatments were also explored. The activation of possible involved signaling pathways were studied after OGD and DMED treatments, along with the addition of inhibitors of these pathways. Finally, the effects of DMED on primary neuronal cells were verified according to the alterations of inflammatory cytokines release and oxidative stress.ResultsDMED obviously increased cell viability and reduced cell apoptosis as well as ratio of Bax/Bcl-2 in OGD-treated PC12 cells. Then, the OGD-induced changes of LDH, MDA, SOD and GSH-Px as well as decreases of neurotrophic factors were all ameliorated by DMED treatment. Key kinases in Notch/NF-κB signaling pathway were up-regulated by OGD, whereas the up-regulations were decreased by DMED. In addition, inhibitor of Notch or NF-κB could augment the effects of DMED on OGD-induced cell injury. Finally, the protective effects of DMED were verified in primary neuronal cells.ConclusionDMED had protective effect on OGD-induced PC12 cell injury, depending on its anti-apoptotic, anti-oxidative activity and the inhibition of Notch/NF-κB activation. Our findings suggested that DMED could be used as a potential therapeutic drug for cerebral ischemia.
Highlights
The present study aims to investigate the protective effects of dexmedetomidine (DMED) on hypoxia ischemia injury induced by oxygen and glucose deprivation (OGD) in PC12 and primary neuronal cells
Effects of DMED on cell viability and apoptosis in PC12 cells under OGD The results in Fig. 1a showed that OGD treatment timedependently decreased the viability of PC12 cells
The results showed that the expression of Bax was significantly increased and the expression of Bcl-2 was significantly decreased after the treatment of OGD at both mRNA and protein levels (p < 0.001)
Summary
The present study aims to investigate the protective effects of dexmedetomidine (DMED) on hypoxia ischemia injury induced by oxygen and glucose deprivation (OGD) in PC12 and primary neuronal cells. Neuronal injury induced by cerebral ischemia is a complex process with various mechanisms, including oxidative stress, apoptosis, activation of kinases and changes in gene expression [5, 6]. Oxidative stress plays a critical role in neuronal injury and has close connections with the pathogenesis of various central nervous system diseases such as cerebral ischemia, Parkinson’s disease and Alzheimer’s disease. Accumulating evidence has reported that oxidative stress could be a therapeutic target of cerebral ischemia [7]. Oxygen-glucose deprivation (OGD) is an in vitro cell model that simulates the in vivo ischemia for exploring the mechanisms
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