Silencing of long non?coding antisense RNA brain?derived neurotrophic factor attenuates hypoxia/ischemia?induced neonatal brain injury

摘要

Hypoxic/ischemic (HI) brain damage (HIBD) is a major cause of acute neonatal brain injury, leading to high mortality and serious neurological deficits. The antisense RNA of brain?derived neurotrophic factor (BDNF?AS) is transcribed from the opposite strand of the BDNF gene. The aim of the present study was to investigate the role of BDNF?AS in HI?induced neuronal cell injury in?vivo and in?vitro. Reverse transcription?quantitative PCR (RT?qPCR) assays indicated that BDNF?AS expression was significantly upregulated in HI?injured neonatal brains and hippocampal neurons. However, BDNF expression was downregulated in HI?injured neonatal brains and hippocampal neurons. Cell Counting Kit?8 assays, Hoechst staining, calcein?AM/PI staining, immunostaining, water maze tests and rotarod tests demonstrated that BDNF?AS silencing protected against hypoxia?induced primary hippocampal neuron injury in?vitro and HI?induced brain injury in?vivo. Mechanistically, RT?qPCR assays and western blotting indicated that BDNF?AS silencing led to increased expression of BDNF and activated the BDNF?mediated signaling pathway, as demonstrated by increased expression levels of BDNF, phosphorylated?Akt and phosphorylated?tropomyosin receptor kinase B. Collectively, the present study provides important insights into the pathogenesis of HIBD, and it was indicated that BDNF?AS silencing may be a promising approach for the treatment of neonatal HIBD.