title: Valproic acid improves outcome after rodent spinal cord injury: potential roles of histone deacetylase inhibition.
abstract: Histone deacetylases (HDAC) inhibitors including valproic acid (VPA) have emerged as a promising therapeutic intervention in neurological disorders. We investigated the levels of acetylated histone and the therapeutic potential of VPA in a rat model of spinal cord injury (SCI). At different time points (12 h, 1 day, 3 days, 1 week and 2 weeks) after SCI or sham surgery, the spinal cords were collected to evaluate the levels of acetylated histone H3 (Ac-H3) and H4 (Ac-H4). VPA or vehicle was injected for 1 week starting immediately after SCI and histone acetylation, apoptosis, as well as neurobehavior were observed to test the effect of VPA. The levels of Ac-H3 and Ac-H4 in the injured spinal cord started to significantly decrease as early as day 1, and remained below those in uninjured controls for at least 2 weeks after SCI. Injection of VPA markedly prevented the reductions of Ac-H3 and Ac-H4, upregulated the expressions of Hsp70 and Bcl-2, reduced apoptosis and finally promoted locomotion recovery. Our data demonstrated that SCI led to marked reduction in histone acetylation; VPA was neuroprotective in the SCI model, and the mechanism may involve HDAC inhibition and protective proteins induction.
authors: Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, PR China.
authors: Lei
authors: L
authors: Lv
authors: Yan
authors: Y
authors: Sun
authors: Xiang
authors: X
authors: Han
authors: Cong-cong
authors: CC
authors: Xu
authors: Yu-Ping
authors: YP
authors: Tang
authors: Qiang
authors: Q
authors: Dong
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects* / Q000201:enzymology* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid; C515890:Hdac1 protein, rat; D056284:Histone Deacetylase 1