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 therapeutic options exist to date. Deficits in motor function are the most visible consequence of SCI. However, 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 histological 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 pharmacological 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 recovery.

中文翻译：

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急性巴氯芬给药促进脊髓损伤后功能恢复

背景语境

创伤性脊髓损伤 (SCI) 会导致严重的运动和感觉功能障碍，从而影响个人和社会行为。医学进步改善了 SCI 患者的支持性治疗措施，但迄今为止还没有有效的神经再生治疗选择。运动功能缺陷是 SCI 最明显的后果。然而，其他并发症，如痉挛，对 SCI 患者的福利产生重大影响。巴氯芬是一种 GABA 激动剂，是治疗痉挛最有效的药物。有趣的是，新出现的数据表明，巴氯芬还可以在 SCI 后发挥神经保护和再生作用。

目的

本研究的目的是了解巴氯芬作为一种促进脊髓损伤后恢复的治疗方法的潜力。

学习规划

我们使用临床前 SCI 小鼠模型，在受伤后的不同时间点给予巴氯芬 1 mg/Kg。

方法

在九周的体内实验期间进行行为分析（运动和膀胱功能）。之后，收集并处理脊髓用于组织学和分子分析。

结果

我们的数据表明，巴氯芬在 SCI 后急性给药可改善小鼠的运动能力。此外，巴氯芬给药还改善了所有实验组的膀胱功能控制。有趣的是，急性巴氯芬给药调节小胶质细胞活化状态和循环趋化因子和细胞因子的水平，表明巴氯芬在调节免疫反应中的推定作用。

结论

尽管必须进行进一步的研究以了解巴氯芬产生的功能改善的基础机制，但我们的数据揭示了巴氯芬促进脊髓损伤后恢复的药理学潜力。

临床相关性

我们的结果表明，巴氯芬是一种众所周知的用于控制痉挛的药物，可在临床前动物模型中改善脊髓损伤后的运动表现。我们的数据为促进 SCI 恢复的药理学策略设计开辟了新途径。