Medical Gas Therapy for Tissue, Organ, and CNS Protection: A Systematic Review of Effects, Mechanisms, and Challenges

Adv Sci (Weinh). 2022 May;9(13):e2104136. doi: 10.1002/advs.202104136. Epub 2022 Mar 4.

Abstract

Gaseous molecules have been increasingly explored for therapeutic development. Here, following an analytical background introduction, a systematic review of medical gas research is presented, focusing on tissue protections, mechanisms, data tangibility, and translational challenges. The pharmacological efficacies of carbon monoxide (CO) and xenon (Xe) are further examined with emphasis on intracellular messengers associated with cytoprotection and functional improvement for the CNS, heart, retina, liver, kidneys, lungs, etc. Overall, the outcome supports the hypothesis that readily deliverable "biological gas" (CO, H2 , H2 S, NO, O2 , O3 , and N2 O) or "noble gas" (He, Ar, and Xe) treatment may preserve cells against common pathologies by regulating oxidative, inflammatory, apoptotic, survival, and/or repair processes. Specifically, CO, in safe dosages, elicits neurorestoration via igniting sGC/cGMP/MAPK signaling and crosstalk between HO-CO, HIF-1α/VEGF, and NOS pathways. Xe rescues neurons through NMDA antagonism and PI3K/Akt/HIF-1α/ERK activation. Primary findings also reveal that the need to utilize cutting-edge molecular and genetic tactics to validate mechanistic targets and optimize outcome consistency remains urgent; the number of neurotherapeutic investigations is limited, without published results from large in vivo models. Lastly, the broad-spectrum, concurrent multimodal homeostatic actions of medical gases may represent a novel pharmaceutical approach to treating critical organ failure and neurotrauma.

Keywords: carbon monoxide; cell signaling; functional recovery; medical gas therapy; spinal cord injury; tissue protection; traumatic brain injury; xenon.

Publication types

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

MeSH terms

  • Carbon Monoxide / metabolism
  • Carbon Monoxide / pharmacology
  • Carbon Monoxide / therapeutic use
  • Gases
  • Pharmaceutical Preparations
  • Phosphatidylinositol 3-Kinases*
  • Xenon* / pharmacology
  • Xenon* / therapeutic use

Substances

  • Gases
  • Pharmaceutical Preparations
  • Xenon
  • Carbon Monoxide