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The Role of GluN2A in Cerebral Ischemia: Promoting Neuron Death and Survival in the Early Stage and Thereafter

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Abstract

Over-activation of NMDA receptors is a crucial step required for brain damage following a stroke. Although clinical trials for NMDA receptor blockers have failed, the role of GluN2A subunit in cerebral ischemia has been extensively evaluated in recent years. However, the effect of GluN2A on neuron damage induced by cerebral ischemia remains a matter of controversy. The underlying reason may be that GluN2A mediates both pro-death and pro-survival effects. These two effects result from two mutually excluding pathways, Ca2+ overload-dependent pro-death signaling and C-terminal-dependent pro-survival signaling, respectively. During the early stage of cerebral ischemia, over-activation of GluN2A plays an important role in Ca2+ overload. Under this condition, pro-death signaling might overcome pro-survival signaling. When GluN2A activity is restored almost to the normal level over time, pro-survival signaling of GluN2A will be dominant. The hypothesis that GluN2A promotes neuron death and survival in the early stage of cerebral ischemia and thereafter will be introduced in detail in this review.

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Authors and Affiliations

  1. Department of Pharmacy, Hebei University of Science and Technology, Yuhua East Road 70, Shijiazhuang, Hebei, 050018, People’s Republic of China

    Yongjun Sun & Zibin Gao

  2. Hebei Research Center of Pharmaceutical and Chemical Engineering, Hebei University of Science and Technology, Shijiazhuang, 050018, People’s Republic of China

    Yongjun Sun & Zibin Gao

  3. North China Pharmaceutical Group New Drug Research and Development Co., Ltd, Shijiazhuang, 050015, People’s Republic of China

    Xiaokun Cheng

  4. School of Nursing, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China

    Jie Hu

  5. State Key Laboratory Breeding Base—Hebei Province Key Laboratory of Molecular Chemistry for Drug, Shijiazhuang, 050018, People’s Republic of China

    Zibin Gao

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  1. Yongjun Sun
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  2. Xiaokun Cheng
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Correspondence to Zibin Gao.

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This work was supported by the Natural Science Foundation of China (NSFC 81200886, NSFC 81402886), the Natural Science Foundation of Hebei Province (H2014208004), the Science and Technology Project of Hebei Province (13397703D), the Key Basic Research Program of the Application Foundation Research Project of Hebei Province (14967719D, 15962704D). The authors acknowledge support from the State Key Laboratory Breeding Base—Hebei Key Laboratory of Molecular Chemistry for Drug and Hebei Research Center of Pharmaceutical and Chemical Engineering.

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Sun, Y., Cheng, X., Hu, J. et al. The Role of GluN2A in Cerebral Ischemia: Promoting Neuron Death and Survival in the Early Stage and Thereafter. Mol Neurobiol 55, 1208–1216 (2018). https://doi.org/10.1007/s12035-017-0395-8

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