Protective Effects of Ferulic Acid against Chronic Cerebral Hypoperfusion-Induced Swallowing Dysfunction in Rats

Int J Mol Sci. 2017 Mar 3;18(3):550. doi: 10.3390/ijms18030550.

Abstract

Ferulic acid (FA), a phenolic phytochemical, has been reported to exert antioxidative and neuroprotective effects. In this study, we investigated the protective effects of FA against the dysfunction of the swallowing reflex induced by ligation of bilateral common carotid arteries (2VO) in rats. In 2VO rats, topical administration of water or citric acid to the pharyngolaryngeal region evoked a diminished number of swallowing events with prolonged latency compared to sham-operated control rats. 2VO rats had an increased level of superoxide anion radical, and decreased dopamine and tyrosine hydroxylase enzyme levels in the striatum, suggesting that 2VO augmented cerebral oxidative stress and impaired the striatal dopaminergic system. Furthermore, substance P (SP) expression in the laryngopharyngeal mucosa, which is believed to be positively regulated by dopaminergic signaling in the basal ganglia, was decreased in 2VO rats. Oral treatment with FA (30 mg/kg) for 3 weeks (from one week before 2VO to two weeks after) improved the swallowing reflex and maintained levels of striatal dopamine and laryngopharyngeal SP expression in 2VO rats. These results suggest that FA maintains the swallowing reflex by protecting the dopamine-SP system against ischemia-induced oxidative damage in 2VO rats.

Keywords: cerebral hypoperfusion; dopaminergic neuron; ferulic acid; oxidative stress; substance P; swallowing dysfunction.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Brain Ischemia / drug therapy
  • Brain Ischemia / etiology*
  • Brain Ischemia / pathology*
  • Brain Ischemia / physiopathology
  • Cerebral Cortex / blood supply*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / pathology*
  • Cerebral Cortex / physiopathology
  • Cerebrovascular Circulation / drug effects
  • Corpus Striatum / blood supply
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Coumaric Acids / pharmacology*
  • Disease Models, Animal
  • Dopamine / biosynthesis
  • Dopaminergic Neurons / metabolism
  • Gene Expression
  • Male
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects
  • Rats
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Coumaric Acids
  • Neuroprotective Agents
  • ferulic acid
  • Tyrosine 3-Monooxygenase
  • Dopamine