Valproic acid improves outcome after rodent spinal cord injury: Potential roles of histone deacetylase inhibition

Therapeutic Potential of Mood Stabilizers Lithium and Valproic Acid: Beyond Bipolar Disorder

“…Anti-inflammation. In a rat pMCAO model, VPA treatment markedly reduced the number of both Ischemic stroke Rat and mouse MCAO models; rat global ischemia model Ren et al, 2004;Kim et al, 2007;Qian et al, 2010;Tsai et al, 2011;Wang et al, 2011aWang et al, , 2012Xuan et LPS-treated midbrain neuron-glia co-cultures; cellular, rat and mouse MPTP models; rotenone-challenged cellular and rat models Peng et al, 2005;Chen et al, 2006Chen et al, , 2007Wu et al, 2008;Castro et al, 2012;Schneider, 2010, 2011;Monti et al, 2010;Xiong et al, 2011 Retinal degeneration Rat retinal ganglion cells; rat retinal ischemia model; optic nerve crush; mice Biermann et al, 2010Biermann et al, , 2011Zhang et al, 2011bZhang et al, , 2012b Spinal cord injury Adult rats and mice; organotypic culture of spinal cord Abematsu et al, 2010;Lv et al, 2011Lv et al, , 2012Penas et al, 2011;Lee et al, 2012b Therapeutic Potential of Mood Stabilizers activated microglia and infiltrating monocytes/macrophages and suppressed ischemia-induced upregulation of proinflammatory factors, inducible nitric oxide synthase, and COX-2 . The antiinflammatory effects of VPA have also been demonstrated in vitro.…”

Regulator of G Protein Signaling 10 (Rgs10) Expression Is Transcriptionally Silenced in Activated Microglia by Histone Deacetylase Activity

“…Blocking either microglial activation or endogenous TLR4 receptors has been shown to attenuate neuropathic pain (Raghavendra et al, 2003;Saito et al, 2010;Sorge et al, 2011;Yoon et al, 2012). Furthermore, enhanced HDAC activity is observed in the spinal cord following nerve injury (Lv et al, 2011;Lu et al, 2013), and HDAC inhibitors reduce inflammatory cytokine release and neuroinflammation (Blanchard and Chipoy, 2005;Lv et al, 2011). Thus, the pSNL model of neuropathic pain is suitable for the in vivo study of molecular signaling pathways in microglia activated by TLR4.…”

The Epigenetic Regulation of Wound Healing

“…63 Antagonism of HDACs has also been shown to be beneficial in the regeneration of other tissues; in mice with spinal cord injuries treated with HDAC inhibitor valproic acid, apoptosis was reduced and functional recovery improved following treatment. 64 In contrast, Taylor and Beck assessed the effect of valproic acid on amphibian tail regeneration, finding that in this model, HDAC inhibition retarded the regenerative process. 65 Whether this variance is due to differences in tissue-specific responsiveness to HDAC manipulation remains to be elucidated; however, this does highlight the dramatic effect that epigenetic modulation may have on tissue repair and proliferation.…”