Sulforaphane activates the cerebral vascular Nrf2-ARE pathway and suppresses inflammation to attenuate cerebral vasospasm in rat with subarachnoid hemorrhage

Brain Res. 2016 Dec 15;1653:1-7. doi: 10.1016/j.brainres.2016.09.035. Epub 2016 Sep 28.


Nrf2-ARE pathway reportedly plays a protective role in several central nervous system diseases. No study has explored the role of the Nrf2-ARE pathway in cerebral vasospasm(CVS) after subarachnoid hemorrhage(SAH). The purpose of the present study was to investigate the activation of the cerebral vascular Nrf2-ARE pathway and to determine the potential role of this pathway in the development of CVS following SAH. We investigated whether the administration of sulforaphane (SFN, a specific Nrf2 activator) modulated vascular caliber, Nrf2-ARE pathway activity, proinflammatory cytokine expression, and clinical behavior in a rat model of SAH. A two-hemorrhage protocol was used to generate an animal model of SAH in male Sprague-Dawley rats. Administration of SFN to these rats following SAH enhanced the activity of the Nrf2-ARE pathway and suppressed the release of proinflammatory cytokines. Vasospasm was markedly attenuated in the basilar arteries after SFN therapy. Additionally, SFN administration significantly ameliorated two behavioral functions disrupted by SAH. These results suggest that SFN has a therapeutic benefit in post-SAH, and this may be due to elevated Nrf2-ARE pathway activity and inhibition of cerebral vascular proinflammatory cytokine expression.

Keywords: Cerebral vasospasm; Inflammation; Nrf2-ARE pathway; Subarachnoid hemorrhage; Sulforaphane.

MeSH terms

  • Animals
  • Appetite / drug effects
  • Appetite / physiology
  • Basilar Artery / drug effects
  • Basilar Artery / metabolism
  • Basilar Artery / pathology
  • Carboxylic Ester Hydrolases / metabolism*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Isothiocyanates / pharmacology*
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • NF-E2-Related Factor 2 / metabolism*
  • Neuroimmunomodulation / drug effects
  • Neuroimmunomodulation / physiology
  • Neuroprotective Agents / pharmacology*
  • Rats, Sprague-Dawley
  • Subarachnoid Hemorrhage / drug therapy*
  • Subarachnoid Hemorrhage / metabolism
  • Subarachnoid Hemorrhage / pathology
  • Sulfoxides
  • Vasodilator Agents / pharmacology
  • Vasospasm, Intracranial / drug therapy*
  • Vasospasm, Intracranial / metabolism
  • Vasospasm, Intracranial / pathology


  • Cytokines
  • Isothiocyanates
  • NF-E2-Related Factor 2
  • Neuroprotective Agents
  • Nfe2l2 protein, rat
  • Sulfoxides
  • Vasodilator Agents
  • Carboxylic Ester Hydrolases
  • arylesterase
  • sulforaphane