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
Current Medicinal Chemistry
Title: Protective Effect of Cyclosporin-A in Spinal Cord Injury: An Overview
Volume: 13 Issue: 22
Author(s): Antonio Ibarra and Araceli Diaz-Ruiz
Affiliation:
Keywords: cNOS, iNOS, methylprednisolone, motor recovery, neuroprotection, nitric oxide, lipid peroxidation
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.
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Cite this article as:
Ibarra Antonio and Diaz-Ruiz Araceli, Protective Effect of Cyclosporin-A in Spinal Cord Injury: An Overview, Current Medicinal Chemistry 2006; 13 (22) . https://dx.doi.org/10.2174/092986706778201503
DOI https://dx.doi.org/10.2174/092986706778201503 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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