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

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Astroglial N-myc downstream-regulated gene 2 protects the brain from cerebral edema induced by stroke.
Glia ( IF 5.4 ) Pub Date : 2020-07-11 , 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}

Affiliation

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.

中文翻译：

星形胶质细胞 N-myc 下游调节基因 2 保护大脑免受中风引起的脑水肿。

脑水肿是脑缺血的严重并发症，是导致脑疝和死亡的主要原因。尽管星形胶质细胞肿胀是细胞毒性水肿的主要诱因，但参与这一过程的分子机制仍然难以捉摸。N-myc 下游调节基因 2 ( NDRG2 ) 是一种经过充分研究的肿瘤抑制基因，主要在哺乳动物大脑的星形胶质细胞中表达。在这里，我们发现 NDRG2 缺乏会导致脑水肿恶化、Na ⁺转移失衡和缺血后星形胶质细胞肿胀。我们还发现星形胶质细胞中 NDRG2 的缺失显着改变了水通道蛋白-4 和 Na ⁺ -K ^{+的表达和分布。}-ATPase β1，与缺血性脑中的细胞极性密切相关。通过挽救NDRG2基因敲除小鼠脑中星形胶质细胞 Na ⁺ ‐K ⁺ ‐ATPase β1的表达可显着缓解脑水肿和星形胶质细胞肿胀。此外，慢病毒构建体对星形胶质细胞 NDRG2 的上调显着减轻了脑水肿、星形胶质细胞肿胀和血脑屏障破坏。我们的结果表明 NDRG2 在维持星形胶质细胞极化以促进 Na ⁺和水转移平衡以及保护大脑免受缺血性水肿方面的特殊作用。这些发现提供了对 NDRG2 作为脑水肿治疗靶点的深入了解。

更新日期：2020-07-11

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