Ambroxol Improves Neuronal Survival and Reduces White Matter Damage through Suppressing Endoplasmic Reticulum Stress in Microglia after Intracerebral Hemorrhage

Biomed Res Int. 2020 Mar 26:2020:8131286. doi: 10.1155/2020/8131286. eCollection 2020.

Abstract

Intracerebral hemorrhage (ICH) has been becoming a serious public health problem. Pneumonia, occurring in 43% of all ICH patients, is a common complication heavily influencing outcome and accounting for more than 1/3 of the overall mortality in patients with ICH. Ambroxol may be an effective additional treatment for ICH patients with pneumonia. But its effect and potential mechanism on functional recovery post-ICH still remain elusive. In the present study, the results indicated that 35 mg/kg and 70 mg/kg ambroxol facilitated neuronal survival and reduced white matter fiber bundle damage due to mitigating microglial activation and reducing proinflammatory cytokine accumulation in mice with ICH. The possible mechanism might be due to suppressing endoplasmic reticulum stress involving the IRE1α/TRAF2 signaling pathway, which paves a new path for the treatment of ICH and opens a new window for the use of ambroxol in clinical practice.

MeSH terms

  • Ambroxol / pharmacology*
  • Animals
  • Cell Death / drug effects*
  • Cell Survival / drug effects*
  • Cerebral Hemorrhage / complications*
  • Disease Models, Animal
  • Endoplasmic Reticulum Stress / physiology*
  • Endoribonucleases / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / metabolism*
  • Neurons / metabolism*
  • Neuroprotective Agents / pharmacology
  • Protein Serine-Threonine Kinases / metabolism
  • White Matter / drug effects*
  • White Matter / metabolism

Substances

  • Neuroprotective Agents
  • Ambroxol
  • Ern1 protein, mouse
  • Protein Serine-Threonine Kinases
  • Endoribonucleases