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Effects of NMDA-Receptor Antagonist on the Expressions of Bcl-2 and Bax in the Subventricular Zone of Neonatal Rats with Hypoxia–Ischemia Brain Damage

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Abstract

Neonatal hypoxia–ischemia brain damage is an important cause of death by affecting prognosis of neural diseases. It is difficult to find effective methods of prevention and treatment due to the complexity of its pathogenesis. N-methyl-d-aspartate (NMDA), as an excitotoxicity amino acids, has proven to play an important role in hypoxic–ischemic. However, the exact effects of the NMDA subunits, NR2A and NR2B, during hypoxic–ischemic have not been investigated in detail. Therefore, we sought to study whether the NMDA receptor antagonist could confer neuroprotective effects in a neonatal rat hypoxia–ischemia model. The effects of intraperitoneal injections of different drugs, namely MK-801 (0.5 mg/kg), NVP-AAM077 (5 mg/kg), and Ro25-6981 (5 mg/kg), on the expressions of anti-apoptotic protein Bcl-2 and apoptosis protein Bax in the subventricular zone were analyzed by immunohistochemical staining to explore the roles of NMDA subunits (NR2A and NR2B) in hypoxic–ischemic. We found that the NR2B antagonist (Ro25-6981) could inhibit hypoxic–ischemic with the increasing Bcl-2 expression. NR2A antagonists (NVP-AAM077) can increase cerebral hypoxia–ischemia in neonatal rats, promoting the expression of apoptotic protein Bax.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 81171141 to Tiejun Xu); this project was funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions.

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The authors declare that they have no conflicts of interest.

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    Authors and Affiliations

    1. Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, Jiangsu, China

      Hongbin Fan, Xiaoquan Li, Wei Wang, Qingwei Lai & Xiaohong Tang

    2. Department of Anatomy and Neurobiology, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221004, Jiangsu, China

      Dianshuai Gao & Tiejun Xu

    3. Department of Clinical Pharmacology, School of Pharmacy, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221004, Jiangsu, China

      Xiaoxing Yin

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    1. Hongbin Fan
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    Correspondence to Xiaoxing Yin or Tiejun Xu.

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    Hongbin Fan and Xiaoquan Li contributed equally to this work.

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    Fan, H., Li, X., Wang, W. et al. Effects of NMDA-Receptor Antagonist on the Expressions of Bcl-2 and Bax in the Subventricular Zone of Neonatal Rats with Hypoxia–Ischemia Brain Damage. Cell Biochem Biophys 73, 323–330 (2015). https://doi.org/10.1007/s12013-015-0586-8

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