Protective Effect of Cyclosporin-A in Spinal Cord Injury: An Overview

Antonio      Ibarra; Araceli      Diaz-Ruiz

Abstract

Cyclosporin-A (CsA) is a potent and selective immunosupressive agent that, due to its mechanism of action, may be used to inhibit both the inflammatory reaction and the synthesis of nitric oxide (NO), a wellknown neurotoxic agent. By these means CsA may diminish overproduction of free radicals and secondarily, lipid peroxidation (LP), both observed after acute spinal cord (SC) injury. Studies performed on reliable experimental models, using a well-standardized CsA dosing scheme, showed that a low dose of this drug inhibits the expression and activity of constitutive and inducible nitric oxide synthases (NOS), two enzymes strongly involved in the production of NO after SCI. Likewise, this compound inhibits LP. This inhibition is equivalent to the one induced by methylprednisolone (MP) at a high dose, but without the deleterious effects of the latter upon the survival of the animals. Moreover, inhibition of LP by CsA significantly correlates with a decrease in the demyelination process at the epicenter of the lesion, a significant survival of neurons in the red nucleus and enhanced motor recovery in animals submitted to a severe SC contusion. CsA acts as a neuroprotector agent after SC injury; hence, this drug may be useful in the treatment of acute SCI. CsA deserves further study in experimental animal models and in humans.

Keywords: cNOS, iNOS, methylprednisolone, motor recovery, neuroprotection, nitric oxide, lipid peroxidation

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