Neuroserpin Protects Rat Neurons and Microglia-Mediated Inflammatory Response Against Oxygen Glucose Deprivation- and Reoxygenation Treatments in an In Vitro Study

作者：Yang, Xuelian; Asakawa, Tetsuya^*; Han, Sha; Liu, Ling; Li, Wei; Wu, Weiwen; Luo, Yunhe; Cao, Wenjie; Cheng, Xin; Xiao, Baoguo; Namba, Hiroki; Lu, Chuanzhen; Dong, Qiang; Wang, Liang^*

来源：Cellular Physiology and Biochemistry, 2016, 38(4): 1472-1482.

DOI：10.1159/000443089

• Neuroserpin
• Oxygen-glucose deprivation
• Neuron
• Microglia
• Neuroprotection

Background/Aims: Neuroserpin (NSP) is known for its neuroprotective role in cerebral ischemic animal models and patients. Our laboratory conducted a series of investigations on the neuroprotection of NSP in different cells in the brain. In the present study, we further observe the effects of NSP on neurons and microglia-mediated inflammatory response following oxygen-glucose deprivation (OGD), and explore possible mechanisms related to neuroprotection of OGD in the central nervous system (CNS). Methods: Neurons and microglia from neonatal rats were treated with OGD followed by reoxygenation (OGD/R). To confirm the effects of NSP, the neuronal survival, neuronal apoptosis, and lactate dehydrogenase (LDH) release were measured in cultured neurons. Furthermore, the levels of IL-1 beta and nitric oxide (NO) release were also detected in cultured microglia. The possible mechanisms for the neuroprotective effect of NSP were explored using Western blot analysis. Results: NSP administration can reverse abnormal variations in neurons and microgliamediated inflammatory response induced by OGD/R processes. The neuronal survival rate, neuronal apoptosis rate, and LDH release were significantly improved by NSP administration in neurons. Simultaneously, the release of IL-1 beta and NO were significantly reduced by NSPin microglia. Western blot showed that the expression of ERK, P38, and JNK was upregulated in microglia by the OGD/R treatment, and these effects were significantly inhibited by NSP. Conclusion: These data verified the neuroprotective effects of NSP on neurons and microglia-mediated inflammatory response. Inhibition of the mitogen-activated protein kinase (MAPK) signaling pathways might playa potential role in NSP neuroprotection on microglia-mediated inflammatory response, which needs further verification.

• 出版日期2016
• 单位上海市浦东新区公利医院; 复旦大学