Carbon monoxide and the CNS: challenges and achievements

Br J Pharmacol. 2015 Mar;172(6):1533-45. doi: 10.1111/bph.12729. Epub 2014 Jul 2.

Abstract

Haem oxygenase (HO) and its product carbon monoxide (CO) are associated with cytoprotection and maintenance of homeostasis in several different organs and tissues. This review focuses upon the role of exogenous and endogenous CO (via HO activity and expression) in various CNS pathologies, based upon data from experimental models, as well as from some clinical data on human patients. The pathophysiological conditions reviewed are cerebral ischaemia, chronic neurodegenerative diseases (Alzheimer's and Parkinson's diseases), multiple sclerosis and pain. Among these pathophysiological conditions, a variety of cellular mechanisms and processes are considered, namely cytoprotection, cell death, inflammation, cell metabolism, cellular redox responses and vasomodulation, as well as the different targeted neural cells. Finally, novel potential methods and strategies for delivering exogenous CO as a drug are discussed, particularly approaches based upon CO-releasing molecules, their limitations and challenges. The diagnostic and prognostic value of HO expression in clinical use for brain pathologies is also addressed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carbon Monoxide / administration & dosage
  • Carbon Monoxide / metabolism*
  • Cell Death / physiology
  • Central Nervous System Diseases / diagnosis
  • Central Nervous System Diseases / physiopathology*
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Homeostasis
  • Humans
  • Prognosis

Substances

  • Carbon Monoxide
  • Heme Oxygenase (Decyclizing)