國家衛生研究院 NHRI:Item 3990099045/7045

NHRI > Institute of Biomedical Engineering and Nanomedicine > Chung-Shi Yang > Periodical Articles > Item 3990099045/7045

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/7045

Title:	Valproic acid attenuates microgliosis in injured spinal cord and purinergic P2X4 receptor expression in activated microglia
Authors:	Lu, WH;Wang, CY;Chen, PS;Wang, JW;Chuang, DM;Yang, CS;Tzeng, SF
Contributors:	Center for Nanomedicine Research
Abstract:	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, P2X4 receptor (P2X4R), has been considered as a potential target to diminish SCI-associated inflammatory responses. In this study, using a minipump-based 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-g 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-treated rats compared with those observed in vehicle-treated 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 P2X4R expression post-SCI. Furthermore, in vitro study indicated that VPA, but not the other HDAC inhibitors, sodium butyrate and trichostatin A (TSA), caused downregulation of P2X4R in microglia activated with lipopolysaccharide (LPS). Moreover, p38 mitogen-activated protein kinase (MAPK)-triggered signaling was involved in the effect of VPA on the inhibition of P2X4R gene expression. In addition to the findings from others, our results also provide important evidence to show the inhibitory effect of VPA on P2X4R expression in activated microglia, which may contribute to reduction of SCI-induced gliosis and subsequently preservation of spinal cord tissues.
Date:	2013-05
Relation:	Journal of Neuroscience Research. 2013 May;91(5):694-705.
Link to:	http://dx.doi.org/10.1002/jnr.23200
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0360-4012&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000315968700008
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84874804934
Appears in Collections:	[Chung-Shi Yang] Periodical Articles

Files in This Item:

File	Description	Size	Format
SCP84873587147.pdf		1445Kb	Adobe PDF	552	View/Open

Loading...