biostudies-literatureWang GHillman Foundation AwardMinistry of Education of the People's Republic of ChinaHHS | NIH | National Institute of Neurological Disorders and StrokeNational Natural Science Foundation of ChinaNINDS NIH HHSState Administration of Foreign Experts AffairsU.S. Department of Veterans Affairs2853-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC4352818biostudies-literatureUnknown112(9)Severe traumatic brain injury (TBI) elicits destruction of both gray and white matter, which is exacerbated by secondary proinflammatory responses. Although white matter injury (WMI) is strongly correlated with poor neurological status, the maintenance of white matter integrity is poorly understood, and no current therapies protect both gray and white matter. One candidate approach that may fulfill this role is inhibition of class I/II histone deacetylases (HDACs). Here we demonstrate that the HDAC inhibitor Scriptaid protects white matter up to 35 d after TBI, as shown by reductions in abnormally dephosphorylated neurofilament protein, increases in myelin basic protein, anatomic preservation of myelinated axons, and improved nerve conduction. Furthermore, Scriptaid shifted microglia/macroProceedings of the National Academy of Sciences of the United States of AmericaHDAC inhibition prevents white matter injury by modulating microglia/macrophage polarization through the GSK3β/PTEN/Akt axis.PMC4352818J1210041NS367368102010802181171149NS4380281000497Research Career Scientist AwardR01 NS036736Hillman Foundation AwardGDW20133100069R01 NS04504881471257NS45048NS45287R01 NS045287201200711100428122800881371306R01 NS043802Chen JHu XBennett MVTang BWang GPu HZheng PLeak RKShi YJiang XGao YLi WWWang YWu YfalseHDAC inhibition prevents white matter injury by modulating microglia/macrophage polarization through the GSK3β/PTEN/Akt axis.Severe traumatic brain injury (TBI) elicits destruction of both gray and white matter, which is exacerbated by secondary proinflammatory responses. Although white matter injury (WMI) is strongly correlated with poor neurological status, the maintenance of white matter integrity is poorly understood, and no current therapies protect both gray and white matter. One candidate approach that may fulfill this role is inhibition of class I/II histone deacetylases (HDACs). Here we demonstrate that the HDAC inhibitor Scriptaid protects white matter up to 35 d after TBI, as shown by reductions in abnormally dephosphorylated neurofilament protein, increases in myelin basic protein, anatomic preservation of myelinated axons, and improved nerve conduction. Furthermore, Scriptaid shifted microglia/macro2015-01-01T00:00:00Z2015 Mar2025-04-18T15:30:02.647Z2019-03-27T01:47:46ZS-EPMC43528182569175010.1073/pnas.1501441112