Role of Acid-Sensing Ion Channel 1a in the Secondary Damage of Traumatic Spinal Cord Injury

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	Role of Acid-Sensing Ion Channel 1a in the Secondary Damage of Traumatic Spinal Cord Injury
	Hu, Rong ; Duan, Bo ; Wang, Dianshi ; Yu, Ye ; Li, Weiguang ; Luo, Haishui ; Lu, Peigang ; Lin, Jiangkai ; Zhu, Gang ; Wan, Qi ; Feng, Hua
刊名	ANNALS OF SURGERY
	2011
卷号	254 期号:2 页码:353-362
关键词	DORSAL-HORN NEURONS VASCULAR MECHANISMS CONTUSION INJURY NERVOUS-SYSTEM MOTOR-NEURONS CELL-DEATH IN-VITRO RAT CONTRIBUTES ISCHEMIA
ISSN号	0003-4932
通讯作者	Feng, H (reprint author), Third Mil Med Univ, Southwest Hosp, Dept Neurosurg, 30 Gao Tanyan St, Chongqing 400038, Peoples R China,fenghua8888@yahoo.com.cn
英文摘要	Objective: To determine the cellular and molecular mechanisms by which acid-sensing ion channel 1a (ASIC1a) plays its role in the secondary injury after traumatic spinal cord injury (SCI), and validate the neuroprotective effect of ASIC1a suppression in SCI model in vivo. Background: Secondary damage after traumatic SCI contributes to the exacerbation of cellular insult and thereby contributes to spinal cord dysfunction. However, the underlying mechanisms remain largely unknown. Acidosis is commonly involved in the secondary injury process after the injury of central nervous system, but whether ASIC1a is involved in secondary injury after SCI is unclear. Methods: Male Sprague-Dawley rats were subjected to spinal contusion using a weight-drop injury approach. Western blotting and immunofluorescence assays were used to observe the change of ASIC1a expression after SCI. The TUNEL staining in vivo as well as the cell viability and death assays in spinal neuronal culture were employed to assess the role of ASIC1a in the secondary spinal neuronal injury. The electrophysiological recording and Ca(2+) imaging were performed to reveal the possible underlying mechanism. The antagonists and antisense oligonucleotide for ASIC1a, lesion volume assessment assay and behavior test were used to estimate the therapeutic effect of ASIC1a on SCI. Results: We show that ASIC1a expression is markedly increased in the periinjury zone after traumatic SCI. Consistent with the change of ASIC1a expression in injured spinal neurons, both ASIC1a-mediated whole-cell currents and ASIC1a-mediated Ca(2+) entry are significantly enhanced after injury. We also show that increased activity of ASIC1a contributes to SCI-induced neuronal death. Importantly, our results indicate that down-regulation of ASIC1a by antagonists or antisense oligonucleotide reduces tissue damage and promotes the recovery of neurological function after SCI. Conclusion: This study reveals a cellular and molecular mechanism by which ASIC1a is involved in the secondary damage process after traumatic SCI. Our results suggest that blockade of Ca(2+)-permeable ASIC1a may be a potential neuroprotection strategy for the treatment of SCI patients.
学科主题	Surgery
收录类别	SCI
资助信息	National Natural Science Foundation of China[30872735, 30830035, 30572167]; 863 Programs (Chinese National Programs for High Technology Research and Development)[2009AA02Z409]; Natural Science Foundation of Chongqing[CSTC2008BA5002, CSTC2008BB5125]
语种	英语
公开日期	2012-07-13
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1532]
专题	上海神经科学研究所_神经所(总)
推荐引用方式 GB/T 7714	Hu, Rong,Duan, Bo,Wang, Dianshi,et al. Role of Acid-Sensing Ion Channel 1a in the Secondary Damage of Traumatic Spinal Cord Injury[J]. ANNALS OF SURGERY,2011,254(2):353-362.
APA	Hu, Rong.,Duan, Bo.,Wang, Dianshi.,Yu, Ye.,Li, Weiguang.,...&Feng, Hua.(2011).Role of Acid-Sensing Ion Channel 1a in the Secondary Damage of Traumatic Spinal Cord Injury.ANNALS OF SURGERY,254(2),353-362.
MLA	Hu, Rong,et al."Role of Acid-Sensing Ion Channel 1a in the Secondary Damage of Traumatic Spinal Cord Injury".ANNALS OF SURGERY 254.2(2011):353-362.