Inhibition of microRNA-181 reduces forebrain ischemia-induced neuronal loss

J Cereb Blood Flow Metab. 2013 Dec;33(12):1976-82. doi: 10.1038/jcbfm.2013.157. Epub 2013 Sep 4.


MicroRNA (miRNA), miR-181a, is enriched in the brain, and inhibition of miR-181a reduced astrocyte death in vitro and infarct volume after stroke in vivo. This study investigated the role of miR-181a in neuronal injury in vitro and hippocampal neuronal loss in vivo after forebrain ischemia. miR-181a levels were altered by transfection with mimic or antagomir. N2a cells subjected to serum deprivation and oxidative stress showed less cell death when miR-181a was reduced and increased death when miR-181a increased; protection was associated with increased Bcl-2 protein. In contrast, transfected primary neurons did not show altered levels of cell death when miR-181a levels changed. Naive male rats and rats stereotactically infused with miR-181a antagomir or control were subjected to forebrain ischemia and cornus ammonis (CA)1 neuronal survival and protein levels were assessed. Forebrain ischemia increased miR-181a expression and decreased Bcl-2 protein in the hippocampal CA1 region. miR-181a antagomir reduced miR-181a levels, reduced CA1 neuronal loss, increased Bcl-2 protein, and significantly prevented the decrease of glutamate transporter 1. Thus, miR-181a antagomir reduced evidence of astrocyte dysfunction and increased CA1 neuronal survival. miR-181a inhibition is thus a potential target in the setting of forebrain or global cerebral ischemia as well as focal ischemia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis
  • Brain / metabolism
  • Brain / pathology*
  • Brain Ischemia / genetics*
  • Brain Ischemia / pathology
  • Brain Ischemia / therapy*
  • Cell Line
  • Cells, Cultured
  • Down-Regulation
  • Excitatory Amino Acid Transporter 2 / metabolism
  • Male
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • Neurons / metabolism
  • Neurons / pathology*
  • Oligonucleotides / genetics
  • Oligonucleotides / therapeutic use*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Transfection


  • Excitatory Amino Acid Transporter 2
  • MIRN181 microRNA, rat
  • MicroRNAs
  • Oligonucleotides
  • Proto-Oncogene Proteins c-bcl-2
  • mirn181 microRNA, mouse