Figure 1.

Potential mechanisms underlying the beneficial effects of melatonin in spinal cord injury (SCI).

Oxidative stress can be induced by free radical generation and lipid peroxidation after SCI. Melatonin may act as a radical scavenger after SCI, as it moderates the increased reactive oxygen species (ROS). Melatonin can also reduce inducible nitric oxide synthase (iNOS) expression and neuroinflammation, and it plays an important role in promoting the repair of damaged blood-spinal cord barrier (BSCB). Furthermore, melatonin can inhibit apoptosis and reduce edema, which are both key elements in the pathogenesis of secondary injury after SCI. Melatonin also plays a protective role by reducing the expression of vascular endothelial growth factor (VEGF), microtubule-associated protein 1A/1B-light chain 3-phosphatidylethanolamine conjugate (LC3 II), cysteine proteases, phospho-p38, and matrix metalloproteinase-9 (MMP-9). Ang1: Angiopoietin 1; AQP4: aquaporin 4; BDNF: brain-derived neurotrophic factor; ED: erectile dysfunction; GAP-43: growth-associated protein-43; GFAP: glial fibrillary acidic protein; IL: interleukin; NFκB: nuclear factor kappaB; NG-2: neuron/glial antigen 2; TNFα: tumor necrosis factor alpha.