title: Valproic acid improves locomotion in vivo after SCI and axonal growth of neurons in vitro.
abstract: Previous studies have found that valproic acid (VPA), a histone deacetylases (HDAC) inhibitor, improves outcomes in a rat model of spinal cord injury (SCI). The study here aimed to further illuminate the neuroprotective effects of VPA against SCI, both in vivo and in vitro. First, spinal cord injury was performed in rats using NYU impactor. Delayed VPA injection (8 h following SCI) significantly accelerated locomotor recovery. VPA therapy also suppressed SCI-induced hypoacetylation of histone and promoted expressions of BDNF and GDNF. Next, the influence of VPA on axonal growth inhibited by a myelin protein was tested. Neurons from embryonic spinal cord or hippocampus were cultured on plates coated with Nogo-A peptide, and escalating concentrations of VPA were added into the cultures. VPA treatment, in a concentration dependent manner, allowed neurons to overcome Nogo-A inhibition of neurite outgrowth. Meanwhile, VPA exposure increased the level of histone acetylation and expression of BDNF in spinal neurons. Cumulatively, these findings indicate that VPA is possibly a promising medication and deserves translational trials for spinal cord injury.
authors.affiliation: Department of Neurology Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200040, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lv
authors.forename: Xiang
authors.initials: X
authors.lastname: Han
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dong
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D005260:Female; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014635:Valproic Acid