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

Abstract

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.