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, 497 (1), 285-291

GAS5 Silencing Protects Against Hypoxia/Ischemia-Induced Neonatal Brain Injury

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GAS5 Silencing Protects Against Hypoxia/Ischemia-Induced Neonatal Brain Injury

Rui-Bin Zhao et al. Biochem Biophys Res Commun.

Abstract

Hypoxic/ischemic brain damage (HIBD) leads to high neonatal mortality and severe neurologic morbidity. However, the molecular mechanism of HIBD in the neonatal infant is still elusive. Long non-coding RNAs are shown as important regulators of brain development and many neurological diseases. Here, we determined the role of long noncoding RNA-GAS5 in HIBD. GAS5 expression was significantly up-regulated in hypoxic/ischemic-injured neonatal brain and hippocampal neurons. GAS5 silencing protected against hypoxic/ischemic-induced brain injury in vivo and primary hippocampal neuron injury in vitro. Mechanistically, GAS5 regulated hippocampal neuron function by sponging miR-23a. Intracerebroventricular injection of GAS5 shRNA significantly decreased brain GAS5 expression, reduced brain infarct size, and improved neurological function recovery. Collectively, this study suggests a promising therapeutic approach of GAS5 inhibition in the treatment of neonatal HIBD.

Keywords: Brain damage; Long noncoding RNA; Therapeutic approach; microRNA sponge.

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