title: Fumaric Acid Esters Attenuate Secondary Degeneration after Spinal Cord Injury.
abstract: Spinal cord injury (SCI) causes permanent changes in motor, sensory, and autonomic functions. Unfortunately, there are no 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 (MS). Investigation has shown not only an 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 the T6-7 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 significant and sustained recovery of motor function. FAEs significantly reduced the severity of inflammation by a modulation of pro-inflammatory cytokines and apoptosis factors, and increased neutrophic factors such as anti-brain-derived neurotrophic factor (BDNF), anti-glial cell-derived neurotrophic factor (GDNF), and neurotrophin-3 (NT3). Our results showed 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.
authors.affiliation: 1 Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina , Messina, Italy .
authors.forename: Marika
authors.initials: M
authors.lastname: Cordaro
authors.affiliation: 1 Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina , Messina, Italy .
authors.forename: Giovanna
authors.initials: G
authors.lastname: Casili
authors.affiliation: 1 Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina , Messina, Italy .
authors.forename: Irene
authors.initials: I
authors.lastname: Paterniti
authors.affiliation: 1 Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina , Messina, Italy .|2 Pharmacological and Physiological Science, Saint Louis University School of Medicine , St. Louis, Missouri.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.affiliation: 1 Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina , Messina, Italy .
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
mesh_terms: D000818:Animals; D005650:Fumarates / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000473:pathology*
chemical_list: D005650:Fumarates; D018696:Neuroprotective Agents
keywords: fumaric acid esters; neuroinflammation; neuroprotection; spinal cord injury