Post-Injury Neuroprotective Effects of the Thalidomide Analog 3,6-Dithiothalidomide on Traumatic Brain Injury

被引:23
作者
Batsaikhan, Buyandelger [1 ]
Wang, Jing-Ya [1 ]
Scerba, Michael T. [2 ]
Tweedie, David [2 ]
Greig, Nigel H. [2 ]
Miller, Jonathan P. [3 ]
Hoffer, Barry J. [3 ]
Lin, Chih-Tung [1 ]
Wang, Jia-Yi [1 ,4 ]
机构
[1] Taipei Med Univ, Coll Med, Grad Inst Med Sci, 250 Wu Xing St, Taipei 11031, Taiwan
[2] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA
[3] Case Western Reserve Univ, Dept Neurol Surg, Cleveland, OH 44106 USA
[4] Taipei Med Univ, Dept Physiol, Sch Med, Coll Med, Taipei 11031, Taiwan
基金
美国国家卫生研究院;
关键词
traumatic brain injury; neurological deficits; 3; 6-dithiothalidomide; neurodegeneration; neuroinflammation; oxidative stress; TUMOR-NECROSIS-FACTOR; CENTRAL-NERVOUS-SYSTEM; FACTOR-ALPHA; TNF-ALPHA; INFLAMMATORY CYTOKINES; PIFITHRIN-ALPHA; INHIBITION; EXPRESSION; 3,6'-DITHIOTHALIDOMIDE; NEUROINFLAMMATION;
D O I
10.3390/ijms20030502
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. Long-term deficits after TBI arise not only from the direct effects of the injury but also from ongoing processes such as neuronal excitotoxicity, inflammation, oxidative stress and apoptosis. Tumor necrosis factor- (TNF-) is known to contribute to these processes. We have previously shown that 3,6-dithiothalidomide (3,6-DT), a thalidomide analog that is more potent than thalidomide with similar brain penetration, selectively inhibits the synthesis of TNF- in cultured cells and reverses behavioral impairments induced by mild TBI in mice. In the present study, we further explored the therapeutic potential of 3,6-DT in an animal model of moderate TBI using Sprague-Dawley rats subjected to controlled cortical impact. A single dose of 3,6-DT (28 mg/kg, i.p.) at 5 h after TBI significantly reduced contusion volume, neuronal degeneration, neuronal apoptosis and neurological deficits at 24 h post-injury. Expression of pro-inflammatory cytokines in the contusion regions were also suppressed at the transcription and translation level by 3,6-DT. Notably, neuronal oxidative stress was also suppressed by 3,6-DT. We conclude that 3,6-DT may represent a potential therapy to ameliorate TBI-induced functional deficits.
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页数:20
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共 62 条
[1]  
Aaltonen KJ, 2012, PLOS ONE, V7, DOI [10.1371/journal.pone.0043508, 10.1371/journal.pone.0030275]
[2]   Cytokines and acute neurodegeneration [J].
Allan, SM ;
Rothwell, NJ .
NATURE REVIEWS NEUROSCIENCE, 2001, 2 (10) :734-744
[3]   Transiently lowering tumor necrosis factor-α synthesis ameliorates neuronal cell loss and cognitive impairments induced by minimal traumatic brain injury in mice [J].
Baratz, Renana ;
Tweedie, David ;
Wang, Jia-Yi ;
Rubovitch, Vardit ;
Luo, Weiming ;
Hoffer, Barry J. ;
Greig, Nigel H. ;
Pick, Chaim G. .
JOURNAL OF NEUROINFLAMMATION, 2015, 12
[4]   Tumor necrosis factor-α synthesis inhibitor, 3,6′-dithiothalidomide, reverses behavioral impairments induced by minimal traumatic brain injury in mice [J].
Baratz, Renana ;
Tweedie, David ;
Rubovitch, Vardit ;
Luo, Weiming ;
Yoon, Jeong Seon ;
Hoffer, Barry J. ;
Greig, Nigel H. ;
Pick, Chaim G. .
JOURNAL OF NEUROCHEMISTRY, 2011, 118 (06) :1032-1042
[5]   Traumatic brain injury and risk of dementia in older veterans [J].
Barnes, Deborah E. ;
Kaup, Allison ;
Kirby, Katharine A. ;
Byers, Amy L. ;
Diaz-Arrastia, Ramon ;
Yaffe, Kristine .
NEUROLOGY, 2014, 83 (04) :312-319
[6]   TNF-α protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation [J].
Belarbi, Karim ;
Jopson, Timothy ;
Tweedie, David ;
Arellano, Carla ;
Luo, Weiming ;
Greig, Nigel H. ;
Rosi, Susanna .
JOURNAL OF NEUROINFLAMMATION, 2012, 9
[7]   INFLAMMATORY CYTOKINES WITHIN THE CENTRAL-NERVOUS-SYSTEM - SOURCES, FUNCTION, AND MECHANISM OF ACTION [J].
BENVENISTE, EN .
AMERICAN JOURNAL OF PHYSIOLOGY, 1992, 263 (01) :C1-C16
[8]  
Blach-Olszewska Zofia, 2007, Neuropsychiatr Dis Treat, V3, P365
[9]   Control of microglial neurotoxicity by the fractalkine receptor [J].
Cardona, Astrid E. ;
Pioro, Erik P. ;
Sasse, Margaret E. ;
Kostenko, Volodymyr ;
Cardona, Sandra M. ;
Dijkstra, Ineke M. ;
Huang, DeRen ;
Kidd, Grahame ;
Dombrowski, Stephen ;
Dutta, RanJan ;
Lee, Jar-Chi ;
Cook, Donald N. ;
Jung, Steffen ;
Lira, Sergio A. ;
Littman, Dan R. ;
Ransohoff, Richard M. .
NATURE NEUROSCIENCE, 2006, 9 (07) :917-924
[10]   Etanercept attenuates traumatic brain injury in rats by reducing early microglial expression of tumor necrosis factor-α [J].
Chio, Chung-Ching ;
Chang, Chin-Hong ;
Wang, Che-Chuan ;
Cheong, Chong-Un ;
Chao, Chien-Ming ;
Cheng, Bor-Chih ;
Yang, Chung-Zhing ;
Chang, Ching-Ping .
BMC NEUROSCIENCE, 2013, 14