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

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 well-known 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.

A pilot study of poly(N-isopropylacrylamide)-g-polyethylene glycol and poly(N-isopropylacrylamide)-g-methylcellulose branched copolymers as injectable scaffolds for local delivery of neurotrophins and cellular transplants into the injured spinal cord

“…As previously mentioned, animals in Group 2, containing PNIPAAm- g -PEG and the cell graft, received treatment with the cyclosporin A immunosuppressant, which reduces T cells and reduces the inflammatory resonse. 17,18,32 The responses were compared with Vitrogen PureCol with BDNF. The IBA-1 staining in Fig.…”

“…Cyclosporin A can also act as a neuroprotective agent after SCI, as it can depress cellular and humoral immune responses by inhibiting T helper lymphocyte proliferation. 17,18,32 …”

Delayed administration of dapsone protects from tissue damage and improves recovery after spinal cord injury

“…This effect is probably reflected in a decrease of cell death mediated by free radicals (Ibarra and Diaz-Ruiz 2006). Previous studies have demonstrated that the use of antioxidant drugs able to inhibit lipid peroxidation attenuates the damage and improves motor function after SCI (Hamada et al, 1996;Diaz-Ruiz et al, 1999Bao et al, 2004).…”

Spinal cord injury sequelae alter drug pharmacokinetics: an overview

“…37 Cyclosporin-A is an immunosuppressant agent that has recently been demonstrated to have neuroprotective and neuroregenerative effects in SCI models. 38 Finally, baclofen is a centrally acting muscle relaxant used to treat spasticity. 31 The absorption of these drugs is significantly reduced when administered orally.…”