GAS5 silencing protects against hypoxia/ischemia-induced neonatal brain injury

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. •GAS5 expression is increased after neonatal hypoxic/ischemic brain injury.•GAS5 knockdown protects hippocampal cells against hypoxic/ischemic stress.•GAS5 regulates hippocampal neuron function by sponging miR-23a.•GAS5 knockdown alleviates hypoxic/ischemic brain injury in vivo.