Acute baclofen administration promotes functional recovery after spinal cord injury

被引:6
作者
Pinho, Andreia G. [1 ,2 ]
Monteiro, Susana [1 ,2 ]
Liberato, Valentina [1 ,2 ]
Santos, Diogo J. [1 ,2 ]
Campos, Jonas [1 ,2 ]
Cibra, Jorge R.
Silva, Nuno A. [1 ,2 ]
de Sousa, Nidia [1 ,2 ]
Barreiro-Iglesias, Anton [3 ]
Salgado, Antonio J. [1 ,2 ,4 ]
机构
[1] Univ Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, P-4710057 Braga, Portugal
[2] ICVS 3Bs Associate Lab, PT Govt Associated Lab, P-4806909 Braga, Portugal
[3] Univ Santiago de Compostela, Fac Biol, Dept Funct Biol, CIBUS, Santiago De Compostela 15782, Spain
[4] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, P-4710057 Braga, Portugal
关键词
Baclofen; Spinal Cord Injury; Functional recovery; GABAergic drugs; Immune response modulation; Neuroinflammation; BLADDER FUNCTION; RECEPTORS;
D O I
10.1016/j.spinee.2022.09.007
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
BACKGROUND CONTEXT: Traumatic spinal cord injury (SCI) leads to severe motor and sensory functional impairments that affect personal and social behaviors. Medical advancements have improved supportive therapeutic measures for SCI patients, but no effective neuroregenerative thera-peutic options exist to date. Deficits in motor function are the most visible consequence of SCI. How-ever, other complications, as spasticity, produce a significant impact on SCI patient's welfare. Baclofen, a GABA agonist, is the most effective drug for spasticity treatment. Interestingly, emerging data reveals that baclofen can also play a role on neuroprotection and regeneration after SCI.PURPOSE: The goal of this study was to understand the potential of baclofen as a treatment to promote recovery after SCI. STUDY DESIGN: We used a pre-clinical SCI mouse model with the administration of baclofen 1 mg/Kg at different time-points after injury.METHODS: Behavior analysis (locomotor and bladder function) were performed during nine weeks of the in vivo experiment. Afterwards, spinal cords were collected and processed for histo-logical and molecular analysis.RESULTS: Our data showed that baclofen leads to locomotor improvements in mice when its administered acutely after SCI. Moreover, baclofen administration also led to improved bladder function control in all experimental groups. Interestingly, acute baclofen administration modulates microglia activation state and levels of circulating chemokines and cytokines, suggesting a putative role of baclofen in the modulation of the immune response. CONCLUSIONS: Although further studies must be performed to understand the mechanisms that underlie the functional improvements produced by baclofen, our data shed light into the pharmaco-logical potential of baclofen to promote recovery after SCI.CLINICAL RELEVANCE: Our outcomes revealed that baclofen, a well-known drug used for spasticity management, improves the motor performance after SCI in a pre-clinical animal model. Our data opens new avenues for pharmacological strategies design to promote SCI recov-ery.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
引用
收藏
页码:379 / 391
页数:13
相关论文
共 28 条
[1]   Molecular mechanisms of the antispasticity effects of baclofen on spinal ventral horn neurons [J].
Abe, Tadakazu ;
Taniguchi, Wataru ;
Nishio, Naoko ;
Nakatsuka, Terumasa ;
Yoshida, Munehito ;
Yamada, Hiroshi .
NEUROREPORT, 2019, 30 (01) :19-25
[2]   Basso mouse scale for locomotion detects differences in recovery after spinal cord in ury in five common mouse strains [J].
Basso, DM ;
Fisher, LC ;
Anderson, AJ ;
Jakeman, LB ;
McTigue, DM ;
Popovich, PG .
JOURNAL OF NEUROTRAUMA, 2006, 23 (05) :635-659
[3]   GABAB receptors Structure, functions, and clinical implications [J].
Benarroch, Eduardo E. .
NEUROLOGY, 2012, 78 (08) :578-584
[4]   Neutrophil Decoys with Anti-Inflammatory and Anti-Oxidative Properties Reduce Secondary Spinal Cord Injury and Improve Neurological Functional Recovery [J].
Bi, Yihui ;
Duan, Wenxiu ;
Chen, Jing ;
You, Tao ;
Li, Shuya ;
Jiang, Wei ;
Li, Min ;
Wang, Gang ;
Pan, Xueyin ;
Wu, Jiang ;
Liu, Dan ;
Li, Jun ;
Wang, Yucai .
ADVANCED FUNCTIONAL MATERIALS, 2021, 31 (34)
[5]   A Longitudinal Study of the Neurologic Safety of Acute Baclofen Use After Spinal Cord Injury [J].
Cragg, Jacquelyn J. ;
Tong, Bobo ;
Jutzeler, Catherine R. ;
Warner, Freda M. ;
Cashman, Neil ;
Geisler, Fred ;
Kramer, John L. K. .
NEUROTHERAPEUTICS, 2019, 16 (03) :858-867
[6]   ANTISPASTICITY DRUGS - MECHANISMS OF ACTION [J].
DAVIDOFF, RA .
ANNALS OF NEUROLOGY, 1985, 17 (02) :107-116
[7]   Role of Baclofen in Modulating Spasticity and Neuroprotection in Spinal Cord Injury [J].
de Sousa, Nidia ;
Santos, Diogo ;
Monteiro, Susana ;
Silva, Nuno ;
Barreiro-Iglesias, Anton ;
Salgado, Antonio J. .
JOURNAL OF NEUROTRAUMA, 2022, 39 (3-4) :249-258
[8]   Methods Used to Evaluate Pain Behaviors in Rodents [J].
Deuis, Jennifer R. ;
Dvorakova, Lucie S. ;
Vetter, Irina .
FRONTIERS IN MOLECULAR NEUROSCIENCE, 2017, 10
[9]   G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences [J].
Faul, Franz ;
Erdfelder, Edgar ;
Lang, Albert-Georg ;
Buchner, Axel .
BEHAVIOR RESEARCH METHODS, 2007, 39 (02) :175-191
[10]   Depletion of microglia exacerbates injury and impairs function recovery after spinal cord injury in mice [J].
Fu, Haitao ;
Zhao, Yanpeng ;
Hu, Die ;
Wang, Song ;
Yu, Tengbo ;
Zhang, Licheng .
CELL DEATH & DISEASE, 2020, 11 (07)