Fumaric Acid Esters Attenuate Secondary Degeneration Following Spinal Cord Injury

Spinal cord injury (SCI) causes permanent changes in motor, sensory and autonomic functions. Unfortunately, there are not a stable cures and current treatments include surgical decompression, methylprednisolone and hemodynamic control that lead to modest function recovery. Fumaric acid esters (FAEs) were firstly used in the management of an immunological skin disorder, such as psoriasis. Because of their potent anti-inflammatory effects, they have been introduced in multiple sclerosis. Investigation shown not only anti-inflammatory, but also supposed neuroprotective mechanism of action. The goal of the present work was to evaluate the potential beneficial effects of dimethyl fumarate (DMF) and monomethyl fumarate (MMF) in a mouse model of traumatic SCI. SCI was produced by extradural compression for 1 min of the spinal cord at T6-T7 level using an aneurysm clip, and DMF and MMF (both at 30 mg/kg) were administered by oral gavage to the mice 1 and 6 h after SCI. For locomotor activity study mice were treated with FAEs once daily for 10 days. We observed that mice treated with DMF exhibited a significantly and sustained recovery of motor function. FAEs significantly reduced the severity of inflammation by a modulation of proinflammatory cytokines and apoptosis factors, and increased neutrophic factors such as BDNF, GDNF and NT-3. Our results showed an important protective effects of DMF in an animal model of SCI, considerably improving recovery of motor function, possibly by reducing the secondary inflammation and tissue injury that characterize this model. DMF may constitute a promising target for future SCI therapies.