2. Academic Validation
  3. Astroglial N-myc downstream-regulated gene 2 protects the brain from cerebral edema induced by stroke

Astroglial N-myc downstream-regulated gene 2 protects the brain from cerebral edema induced by stroke

  • Glia. 2021 Feb;69(2):281-295. doi: 10.1002/glia.23888.
Hang Guo 1 2,  Anqi Yin 2 3,  Yulong Ma 4,  Ze Fan 2,  Liang Tao 2,  Wenhong Tang 5,  Yaqun Ma 1,  Wugang Hou 2,  Guohong Cai 6,  Lixia Zhuo 7,  Jian Zhang 8,  Yan Li 2 7,  Lize Xiong 2 9
Affiliations

Affiliations

  • 1 Department of Anesthesiology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, China.
  • 2 Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Air Force Military Medical University, Xi'an, China.
  • 3 Department of Anesthesiology, Jinling Hospital, Nanjing, China.
  • 4 Anesthesia and Operation Center, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
  • 5 Department of Anesthesiology, The 960th Hospital of PLA, Jinan, China.
  • 6 Institute of Neuroscience, The Air Force Military Medical University, Xi'an, China.
  • 7 Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • 8 Department of Biochemistry and Molecular Biology, The Air Force Military Medical University, Xi'an, China.
  • 9 Department of Anesthesiology & Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai, China.
PMID: 32652708 DOI: 10.1002/glia.23888
Abstract

Brain edema is a grave complication of brain ischemia and is the main cause of herniation and death. Although astrocytic swelling is the main contributor to cytotoxic edema, the molecular mechanism involved in this process remains elusive. N-myc downstream-regulated gene 2 (NDRG2), a well-studied tumor suppressor gene, is mainly expressed in astrocytes in mammalian brains. Here, we found that NDRG2 deficiency leads to worsened cerebral edema, imbalanced Na+ transfer, and astrocyte swelling after ischemia. We also found that NDRG2 deletion in astrocytes dramatically changed the expression and distribution of aquaporin-4 and Na+ -K+ -ATPase β1, which are strongly associated with cell polarity, in the ischemic brain. Brain edema and astrocyte swelling were significantly alleviated by rescuing the expression of astrocytic Na+ -K+ -ATPase β1 in NDRG2-knockout mouse brains. In addition, the upregulation of astrocytic NDRG2 by lentiviral constructs notably attenuated brain edema, astrocytic swelling, and blood-brain barrier destruction. Our results indicate a particular role of NDRG2 in maintaining astrocytic polarization to facilitate Na+ and water transfer balance and to protect the brain from ischemic edema. These findings provide insight into NDRG2 as a therapeutic target in cerebral edema.

Keywords

N-myc downstream-regulated gene 2; astrocytes; blood-brain barrier; brain edema; ischemic stroke.

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