Potential of immunosuppressive agents in cerebral ischaemia

Indian J Med Res. 2011 Jan;133(1):15-26.

Abstract

Ischaemic stroke is a disorder involving multiple mechanisms of injury progression including activation of glutamate receptors, release of proinflammatory cytokines, nitric oxide (NO), free oxygen radicals and proteases. Presently, recombinant tissue plasminogen activator (rtPA) is the only drug approved for the management of acute ischaemic stroke. This drug, however, is associated with limitations like narrow therapeutic window and increased risk of intracranial haemorrhage. A large number of therapeutic agents have been tested including N-methyl-D-aspartate (NMDA) receptor antagonist, calcium channel blockers and antioxidants for management of stroke, but none has provided significant neuroprotection in clinical trials. Therefore, searching for other potentially effective drugs for ischaemic stroke management becomes important. Immunosuppressive agents with their wide array of mechanisms have potential as neuroprotectants. Corticosteroids, immunophilin ligands, mycophenolate mofetil and minocycline have shown protective effect on neurons by their direct actions or attenuating toxic effects of mediators of inflammation. This review focuses on the current status of corticosteroids, cyclosporine A, FK506, rapamycin, mycophenolate mofetil and minocycline in the experimental models of cerebral ischaemia.

Publication types

  • Review

MeSH terms

  • Brain Ischemia / drug therapy*
  • Brain Ischemia / pathology
  • Cell Death / physiology
  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Neuroprotective Agents / therapeutic use
  • Steroids / therapeutic use
  • Stroke / drug therapy*
  • Stroke / pathology
  • Tissue Plasminogen Activator / therapeutic use

Substances

  • Fibrinolytic Agents
  • Immunosuppressive Agents
  • Neuroprotective Agents
  • Steroids
  • Tissue Plasminogen Activator