{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:24:55Z","timestamp":1790904295676,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,2,13]],"date-time":"2013-02-13T00:00:00Z","timestamp":1360713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Peripheral injection with a high dose of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, into animals with mild or moderate spinal cord injury (SCI) for 1 week can reduce spinal cord tissue loss and promote hindlimb locomotor recovery. A purinergic adenosine triphosphate (ATP) receptor subtype, P2X<jats:sub>4<\/jats:sub> receptor (P2X<jats:sub>4<\/jats:sub>R), has been considered as a potential target to diminish SCI\u2010associated inflammatory responses. In this study, using a minipump\u2010based infusion system, we found that intraspinal infusion with VPA for 3 days into injured spinal cord significantly improved hindlimb locomotion of rats with severe SCI induced by a 10\u2010g NYU impactor dropping from the height of 50 mm onto the spinal T9\/10 segment. The neuronal fibers in the injured spinal cord tissues were significantly preserved in VPA\u2010treated rats compared with those observed in vehicle\u2010treated animals. Moreover, the accumulation of microglia\/macrophages and astrocytes in the injured spinal cord was attenuated in the animal group receiving VPA infusion. VPA also significantly reduced P2X<jats:sub>4<\/jats:sub>R expression post\u2010SCI. Furthermore, in vitro study indicated that VPA, but not the other HDAC inhibitors, sodium butyrate and trichostatin A (TSA), caused downregulation of P2X<jats:sub>4<\/jats:sub>R in microglia activated with lipopolysaccharide (LPS). Moreover, p38 mitogen\u2010activated protein kinase (MAPK)\u2010triggered signaling was involved in the effect of VPA on the inhibition of P2X<jats:sub>4<\/jats:sub>R gene expression. In addition to the findings from others, our results also provide important evidence to show the inhibitory effect of VPA on P2X<jats:sub>4<\/jats:sub>R expression in activated microglia, which may contribute to reduction of SCI\u2010induced gliosis and subsequently preservation of spinal cord tissues. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23200","type":"journal-article","created":{"date-parts":[[2013,2,13]],"date-time":"2013-02-13T12:05:45Z","timestamp":1360757145000},"page":"694-705","source":"Crossref","is-referenced-by-count":42,"title":["Valproic acid attenuates microgliosis in injured spinal cord and purinergic P2X<sub>4<\/sub> receptor expression in activated microglia"],"prefix":"10.1002","volume":"91","author":[{"given":"Wen\u2010Hsin","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih\u2010Yen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po\u2010See","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010Wen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De\u2010Maw","family":"Chuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung\u2010Shi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun\u2010Fen","family":"Tzeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,2,13]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"90","article-title":"Effects of valproic acid, a histone deacetylase inhibitor, on improvement of locomotor function in rat spinal cord injury based on epigenetic science","volume":"16","author":"Abdanipour A","year":"2012","journal-title":"Iranian Biomed J"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42957"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2003.08.004"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1995.12.1"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1996.13.343"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05387.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019052-200206000-00021"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-3903"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0272-0590(88)90112-1"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.2.172"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00074.2001"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001893"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.06.053"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10303"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(02)80061-3"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2009.06.002"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1994.80.1.0097"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-009-9138-2"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4930-11.2012"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2005.10.004"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2008.11.003"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.37.3.379"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.06409.x"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1928"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.08.024"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2001.7628"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)02439-7"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2005.07.001"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04824.x"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2009.10.003"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612053507468"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1229"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.120188"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2004.02.006"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2012.07731.x"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(00)01559-7"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e318166b822"},{"key":"e_1_2_6_39_1","first-page":"255","article-title":"Serum protein binding and pharmacokinetics of valproate in man, dog, rat and mouse","volume":"204","author":"Loscher W","year":"1978","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2011.11.042"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.03.040"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.85.3.890"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2007.08.007"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5512-08.2009"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10215"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2005.07.003"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2011.01.012"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbrainres.2004.10.021"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101287200"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1999.00792.x"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2005.02.016"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00626.x"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-006-0074-5"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5714-08.2009"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01786"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2004.12.002"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/1423-0127-18-13"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1082"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2008.07.050"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2010.07.004"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.3340\/jkns.2012.51.4.191"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjnr.23200","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.23200","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T06:59:30Z","timestamp":1697525970000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.23200"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,13]]},"references-count":60,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2013,5]]}},"alternative-id":["10.1002\/jnr.23200"],"URL":"https:\/\/doi.org\/10.1002\/jnr.23200","archive":["Portico"],"relation":{},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,13]]}}}