期刊
NEUROCHEMISTRY INTERNATIONAL
卷 94, 期 -, 页码 23-31出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2016.02.002
关键词
Traumatic brain injury; Neurons; NKCC1; Erk; Apoptosis
资金
- National Natural Science Foundation of China [81430043, 81200949, 30930093]
- National Science and Technology Major Project of China [2013ZX09J13109-02C]
- National Science and Technology Pillar Program of China [2012BAI11B02]
- Science and Technology Project of Shaanxi [2013KTCQ03-01]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT-14208]
- Key Project of the Twelfth Five-year Plan of Scientific Research of China [AWS11J008]
Traumatic brain injury (TBI) is the leading cause of mortality and morbidity worldwide and is characterized by immediate brain damage and secondary injuries, such as brain edema and ischemia. However, the exact pathological mechanisms that comprise these associated secondary injuries have not been fully elucidated. This study aimed to investigate the role of the Na+-K+-2Cl(-) cotransporter-1 (NKCC1) in the disruption of ion homeostasis and neuronal apoptosis in TBI. Using a traumatic neuron injury (TNI) model in vitro and a controlled cortex injury (CCI) model in vivo, the present study investigated changes in the expression and effects of NKCC1 in TBI using western blot, RNA interference, a lactate dehydrogenase (LDH) release assay, TdT-mediated dUTP Nick end-labeling (TUNEL) analysis, sodium imaging, brain water content, and neurological severity scoring. TBI induced the expression of NKCC1 to be significantly upregulated in the cortex, both in vitro and in vivo. Pharmacological inhibitor bumetanide (Bume) or NKCC1 RNA interference significantly attenuated TBI-induced intracellular Na+ increase, inhibited neuronal apoptosis, and improved brain edema and neurological function. Furthermore, NKCC1 inhibition also significantly inhibited TBI-induced extracellular signal-regulated kinase (Erk) activation. Erk inhibition significantly protected neurons from TBI injury; however, Erk inhibition had no effect on NKCC1 expression or the neuroprotective effect of NKCC1 inhibition against TBI. This study demonstrates the role of NKCC1 in MI-induced brain cortex injury, establishing that NKCC1 may play a neurotoxic role in TBI and that the inhibition of NKCC1 may protect neurons from TBI via the regulation of Erk signaling. (C) 2016 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据