Cyclosporine A, a Potential Therapy of Ischemic Reperfusion Injury. A Common History for Heart and Brain

Cerebrovasc Dis. 2016;42(5-6):309-318. doi: 10.1159/000446850. Epub 2016 Jun 1.

Abstract

Background: Ischemic stroke (IS) and acute myocardial infarction require emergency reperfusion tissue in order to improve functional outcome. Intra-arterial thrombectomy recently showed very encouraging improvement in IS patients' outcome. However, endovascular methods enhancing reperfusion may expose patients to increase in ischemic reperfusion injury. Experimental evidence indicates that brain ischemic reperfusion injury may be attenuated by ischemic pre- and postconditioning. The opening of mitochondrial permeability transition pore plays a critical role in the onset of reperfusion damage. This mechanism can be inhibited by immunosuppressive drugs like cyclosporine A (CsA).

Summary: In this review, we present existing experimental and clinical data suggesting that conditioning interventions may prevent brain ischemic reperfusion injury and future challenge for neuroprotection by CsA in acute IS. Key Messages: The concept of conditioning has been recently investigated clinically but to a lesser extent in the realm of IS. Recent experimental and phase II clinical research has suggested potential neuroprotective properties of cyclosporine; however, further larger clinical trials are needed to demonstrate that CsA improves clinical outcome in acute IS patients.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Brain / physiopathology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology
  • Cyclosporine / therapeutic use*
  • Disease Models, Animal
  • Humans
  • Mitochondrial Membrane Transport Proteins / agonists
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Permeability Transition Pore
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / physiopathology
  • Neuroprotective Agents / therapeutic use*
  • Signal Transduction / drug effects
  • Stroke / drug therapy*
  • Stroke / metabolism
  • Stroke / pathology
  • Stroke / physiopathology

Substances

  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Neuroprotective Agents
  • Cyclosporine