Effect of intravenous injection of antagomiR-1 on brain ischemia

Mol Biol Rep. 2019 Feb;46(1):1149-1155. doi: 10.1007/s11033-018-04580-y. Epub 2019 Feb 1.

Abstract

Stroke is one of the leading causes of death in the world, but the underlying molecular mechanism of this disease remains elusive, thus it will be great challenges to finding appropriate protection. MicroRNAs are short, single-stranded, non-coding RNAs and recent studies have shown that they are aberrantly expressed in ischemic condition. Due to the fact that miR-1 has harmful effects on neural damages during brain ischemia, limited miR-1 has been proven to be protective in middle cerebral artery occlusion (MCAO). Here, the possible positive effect of intravenous injection of antagomiR-1 as a post-ischemic treatment on neurological deficits, infarct volume, brain edema and blood-brain barrier (BBB) permeability was evaluated. The rats were divided randomly into three experimental groups, each with 21 animals. MCAO surgery was performed on all groups and one hour later, 0.1 ml normal saline, 0.1 ml rapamycin and 300 pmol/g miR-1 antagomir (soluble in 0.1 ml normal saline), were injected intravenously into control, positive control and treatment group, respectively. After 24 h, neurologic deficits score, infarct volume, brain edema and BBB permeability were measured. The results indicated that post-treatment with miR-1 antagomir significantly improved neurological deficits and reduced infarction volume, brain edema, and BBB permeability. These data proved that there is a positive effects of antagomiR-1 on ischemic neuronal injury and neurological impairment. Due to the fact that microRNAs are able to protect the brain, it would be a promising therapeutic approach to stroke treatment.

Keywords: AntagomiR; BBB; Edema; Infarct volume; NDS; Stroke; miR-1.

MeSH terms

  • Administration, Intravenous / methods
  • Animals
  • Antagomirs / genetics
  • Antagomirs / therapeutic use*
  • Blood-Brain Barrier / pathology
  • Brain / drug effects
  • Brain Ischemia / genetics
  • Brain Ischemia / therapy*
  • Disease Models, Animal
  • Infarction, Middle Cerebral Artery / genetics
  • Infarction, Middle Cerebral Artery / therapy
  • Male
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics
  • Neurons / drug effects
  • Rats
  • Rats, Wistar
  • Sirolimus / therapeutic use
  • Stroke / therapy

Substances

  • Antagomirs
  • MIRN1 microRNA, human
  • MicroRNAs
  • Sirolimus