Nicotinamide mononucleotide attenuates brain injury after intracerebral hemorrhage by activating Nrf2/HO-1 signaling pathway

Sci Rep. 2017 Apr 6;7(1):717. doi: 10.1038/s41598-017-00851-z.


Replenishment of NAD+ has been shown to protect against brain disorders such as amyotrophic lateral sclerosis and ischemic stroke. However, whether this intervention has therapeutic effects in intracerebral hemorrhage (ICH) is unknown. In this study, we sought to determine the potential therapeutic value of replenishment of NAD+ in ICH. In a collagenase-induced ICH (cICH) mouse model, nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide (NAD+) biosynthesis, was administrated at 30 minutes post cICH from tail vein to replenish NAD+. NMN treatment did not decrease hematoma volume and hemoglobin content. However, NMN treatment significantly reduced brain edema, brain cell death, oxidative stress, neuroinflammation, intercellular adhesion molecule-1 expression, microglia activation and neutrophil infiltration in brain hemorrhagic area. Mechanistically, NMN enhanced the expression of two cytoprotective proteins: heme oxygenase 1 (HO-1) and nuclear factor-like 2 (Nrf2). Moreover, NMN increased the nuclear translocation of Nrf2 for its activation. Finally, a prolonged NMN treatment for 7 days markedly promoted the recovery of body weight and neurological function. These results demonstrate that NMN treats brain injury in ICH by suppressing neuroinflammation/oxidative stress. The activation of Nrf2/HO-1 signaling pathway may contribute to the neuroprotection of NMN in ICH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Brain Injuries / drug therapy
  • Brain Injuries / etiology*
  • Brain Injuries / metabolism*
  • Brain Injuries / pathology
  • Cell Death / drug effects
  • Cerebral Hemorrhage / complications*
  • Disease Models, Animal
  • Heme Oxygenase-1 / metabolism*
  • Immunohistochemistry
  • Inflammation Mediators / metabolism
  • Mice
  • Microglia / metabolism
  • NAD / metabolism
  • NF-E2-Related Factor 2 / metabolism*
  • Neuroprotection / drug effects
  • Neutrophil Infiltration
  • Nicotinamide Mononucleotide / pharmacology*
  • Oxidative Stress / drug effects
  • Protective Agents / pharmacology
  • Signal Transduction / drug effects*
  • Time Factors


  • Biomarkers
  • Inflammation Mediators
  • NF-E2-Related Factor 2
  • Protective Agents
  • NAD
  • Nicotinamide Mononucleotide
  • Heme Oxygenase-1