Cyclosporine-A as a neuroprotective agent against stroke: its translation from laboratory research to clinical application

Neuropeptides. 2011 Dec;45(6):359-68. doi: 10.1016/j.npep.2011.04.002. Epub 2011 May 17.

Abstract

Stoke remains a leading cause of death and disability with limited treatment options. Extensive research has been aimed at studying cell death events that accompany stroke and how to use these same cell death pathways as potential therapeutic targets for treating the disease. The mitochondrial permeability transition pore (MPTP) has been implicated as a major factor associated with stroke-induced neuronal cell death. MPTP activation and increased permeability has been shown to contribute to the events that lead to cell death. Cyclosporine A (CsA), a widely used immunosuppressant in transplantation and rheumatic medicine, has been recently shown to possess neuroprotective properties through its ability to block the MPTP, which in turn inhibits neuronal damage. This newfound CsA-mediated neuroprotection pathway prompted research on its use to prevent cell death in stroke and other neurological conditions. Preclinical studies are being conducted in hopes of establishing the safety and efficacy guidelines for CsA use in human trials as a potential neuroprotective agent against stroke. In this review, we provide an overview of the current laboratory and clinical status of CsA neuroprotection.

Publication types

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

MeSH terms

  • Animals
  • Brain Injuries / drug therapy
  • Cell Death / drug effects
  • Clinical Trials as Topic
  • Cyclosporine / chemistry
  • Cyclosporine / pharmacology
  • Cyclosporine / therapeutic use*
  • Humans
  • Immunosuppressive Agents / chemistry
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Mitochondria / drug effects
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Molecular Structure
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Stroke / drug therapy*
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Mitochondrial Membrane Transport Proteins
  • Neuroprotective Agents
  • mitochondrial permeability transition pore
  • Cyclosporine