Baclofen modulates the immune response after spinal cord injury with locomotor benefits

IF 7.7 2区 医学 Q1 PHARMACOLOGY & PHARMACY British Journal of Pharmacology Pub Date : 2025-01-22 DOI:10.1111/bph.17438
Nídia de Sousa, Ariana Correia-Silva, Andreia G. Pinho, André Vidinha-Mira, Laura Cainé, Marta F. Lima, Diogo J. Santos, Jorge R. Cibrão, Jonas Campos, Helena Cavaleiro, Tiffany S. Pinho, João L. Afonso, Belém Sampaio-Marques, Susana Monteiro, Nuno A. Silva, Antón Barreiro-Iglesias, António J. Salgado
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Abstract

Background and Purpose

Spinal cord injury (SCI) is a neurological condition that affects motor and sensory functions below the injury site. The consequences of SCI are devastating for the patients, and although significant efforts have been done in the last years, there is no effective therapy. Baclofen has emerged in the last few years as an interesting drug in the SCI field. Already used in the SCI clinical setting to control spasticity, baclofen has shown important impact on SCI recovery in animal models, such as lampreys and mice.

Experimental Approach and Key Results

Herein, we proposed to go deeper into baclofen’s mechanism of action and to study its role on the modulation of the immune response after SCI, a major process associated with the severeness of the lesion. Using a SCI compression mice model, we confirmed that baclofen leads to higher locomotor performance, but only at 1 mg·kg−1 and not in higher concentrations, as 5 mg·kg−1. Moreover, we found that baclofen at 1 mg·kg−1 can strongly modulate the immune response after SCI at local, systemic and peripheric levels. This is interesting and intriguingly at the same time, since now, additional studies should be performed to understand if the modulation of the immune response is the responsible for the locomotor outcomes observed on Baclofen treated animals.

Conclusion and Implications

Our findings showed, for the first time, that baclofen can modulate the immune response after SCI, becoming a relevant drug in the field of the immunomodulators.

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巴氯芬调节脊髓损伤后的免疫反应与运动益处。
背景与目的:脊髓损伤是一种影响损伤部位以下运动和感觉功能的神经系统疾病。脊髓损伤的后果对患者来说是毁灭性的,尽管在过去的几年里已经做了很大的努力,但没有有效的治疗方法。巴氯芬近年来作为一种有趣的药物出现在脊髓损伤领域。巴氯芬已被用于脊髓损伤的临床治疗,用于控制痉挛,并在七鳃鳗和小鼠等动物模型中显示出对脊髓损伤恢复的重要影响。实验方法及关键结果:我们拟深入研究巴氯芬的作用机制,研究其在脊髓损伤后免疫反应调节中的作用,这是与损伤严重程度相关的一个重要过程。通过脊髓损伤小鼠模型,我们证实巴氯芬可以提高运动能力,但仅在1 mg·kg-1时有效,而在5 mg·kg-1时无效。此外,我们发现1 mg·kg-1的巴氯芬可以在局部、全身和外周水平上强烈调节脊髓损伤后的免疫反应。这是有趣和有趣的,同时,从现在开始,应该进行更多的研究来了解免疫反应的调节是否对巴氯芬治疗动物的运动结果负责。结论和意义:我们的研究结果首次表明巴氯芬可以调节脊髓损伤后的免疫反应,成为免疫调节剂领域的相关药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
15.40
自引率
12.30%
发文量
270
审稿时长
2.0 months
期刊介绍: The British Journal of Pharmacology (BJP) is a biomedical science journal offering comprehensive international coverage of experimental and translational pharmacology. It publishes original research, authoritative reviews, mini reviews, systematic reviews, meta-analyses, databases, letters to the Editor, and commentaries. Review articles, databases, systematic reviews, and meta-analyses are typically commissioned, but unsolicited contributions are also considered, either as standalone papers or part of themed issues. In addition to basic science research, BJP features translational pharmacology research, including proof-of-concept and early mechanistic studies in humans. While it generally does not publish first-in-man phase I studies or phase IIb, III, or IV studies, exceptions may be made under certain circumstances, particularly if results are combined with preclinical studies.
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