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Sovateltide(ILR-1620)改善脊髓损伤大鼠模型的运动功能并减轻痛觉过敏。

Sovateltide (ILR-1620) Improves Motor Function and Reduces Hyperalgesia in a Rat Model of Spinal Cord Injury.

机构信息

First Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Department of Neurology, Tallaght University Hospital (TUH)/The Adelaide and Meath Hospital, Dublin, Incorporating the National Children's Hospital (AMNCH), Dublin, Ireland.

出版信息

Neurocrit Care. 2024 Oct;41(2):455-468. doi: 10.1007/s12028-024-01950-2. Epub 2024 Mar 5.


DOI:10.1007/s12028-024-01950-2
PMID:38443708
Abstract

BACKGROUND: Spinal cord injury (SCI) presents a major global health challenge, with rising incidence rates and substantial disability. Although progress has been made in understanding SCI's pathophysiology and early management, there is still a lack of effective treatments to mitigate long-term consequences. This study investigates the potential of sovateltide, a selective endothelin B receptor agonist, in improving clinical outcomes in an acute SCI rat model. METHODS: Thirty male Sprague-Dawley rats underwent sham surgery (group A) or SCI and treated with vehicle (group B) or sovateltide (group C). Clinical tests, including Basso, Beattie, and Bresnahan scoring, inclined plane, and allodynia testing with von Frey hair, were performed at various time points. Statistical analyses assessed treatment effects. RESULTS: Sovateltide administration significantly improved motor function, reducing neurological deficits and enhancing locomotor recovery compared with vehicle-treated rats, starting from day 7 post injury. Additionally, the allodynic threshold improved, suggesting antinociceptive properties. Notably, the sovateltide group demonstrated sustained recovery, and even reached preinjury performance levels, whereas the vehicle group plateaued. CONCLUSIONS: This study suggests that sovateltide may offer neuroprotective effects, enhancing neurogenesis and angiogenesis. Furthermore, it may possess anti-inflammatory and antinociceptive properties. Future clinical trials are needed to validate these findings, but sovateltide shows promise as a potential therapeutic strategy to improve functional outcomes in SCI. Sovateltide, an endothelin B receptor agonist, exhibits neuroprotective properties, enhancing motor recovery and ameliorating hyperalgesia in a rat SCI model. These findings could pave the way for innovative pharmacological interventions for SCI in clinical settings.

摘要

背景:脊髓损伤(SCI)是一个全球性的主要健康挑战,发病率不断上升,导致大量残疾。尽管在理解 SCI 的病理生理学和早期管理方面已经取得了进展,但仍缺乏有效的治疗方法来减轻长期后果。本研究调查了选择性内皮素 B 受体激动剂 sovateltide 在改善急性 SCI 大鼠模型临床结果方面的潜力。

方法:30 只雄性 Sprague-Dawley 大鼠接受假手术(A 组)或 SCI 并接受载体(B 组)或 sovateltide(C 组)治疗。在不同时间点进行临床测试,包括 Basso、Beattie 和 Bresnahan 评分、斜面和 von Frey 毛发的痛觉过敏测试。统计分析评估了治疗效果。

结果:与载体治疗的大鼠相比,sovateltide 给药显著改善了运动功能,减少了神经功能缺损并增强了运动恢复,从损伤后第 7 天开始。此外,痛觉过敏阈值改善,表明具有抗伤害感受作用。值得注意的是,sovateltide 组表现出持续的恢复,甚至达到了受伤前的水平,而载体组则趋于平稳。

结论:本研究表明,sovateltide 可能具有神经保护作用,增强神经发生和血管生成。此外,它可能具有抗炎和抗伤害感受作用。需要进行未来的临床试验来验证这些发现,但 sovateltide 作为一种潜在的治疗策略,有望改善 SCI 的功能结果。内皮素 B 受体激动剂 sovateltide 表现出神经保护特性,可增强运动恢复并改善大鼠 SCI 模型中的痛觉过敏。这些发现为临床环境中针对 SCI 的创新药理学干预铺平了道路。

相似文献

[1]
Sovateltide (ILR-1620) Improves Motor Function and Reduces Hyperalgesia in a Rat Model of Spinal Cord Injury.

Neurocrit Care. 2024-10

[2]
Neuroprotective Effect of Sovateltide (IRL 1620, PMZ 1620) in a Neonatal Rat Model of Hypoxic-Ischemic Encephalopathy.

Neuroscience. 2022-1-1

[3]
Administration of ONO-2506 suppresses neuropathic pain after spinal cord injury by inhibition of astrocytic activation.

Spine J. 2019-4-8

[4]
Administration of low dose estrogen attenuates persistent inflammation, promotes angiogenesis, and improves locomotor function following chronic spinal cord injury in rats.

J Neurochem. 2016-5

[5]
Low-energy extracorporeal shock wave therapy promotes vascular endothelial growth factor expression and improves locomotor recovery after spinal cord injury.

J Neurosurg. 2014-12

[6]
Eugenol promotes functional recovery and alleviates inflammation, oxidative stress, and neural apoptosis in a rat model of spinal cord injury.

Restor Neurol Neurosci. 2018

[7]
Low-energy extracorporeal shock wave therapy for promotion of vascular endothelial growth factor expression and angiogenesis and improvement of locomotor and sensory functions after spinal cord injury.

J Neurosurg Spine. 2016-12

[8]
Timing and duration of anti-alpha4beta1 integrin treatment after spinal cord injury: effect on therapeutic efficacy.

J Neurosurg Spine. 2009-11

[9]
Effects of early surgical decompression on functional and histological outcomes after severe experimental thoracic spinal cord injury.

J Neurosurg Spine. 2017-1

[10]
Simvastatin inhibits neural cell apoptosis and promotes locomotor recovery via activation of Wnt/β-catenin signaling pathway after spinal cord injury.

J Neurochem. 2016-7

本文引用的文献

[1]
Spinal Cord Injury: The Global Incidence, Prevalence, and Disability From the Global Burden of Disease Study 2019.

Spine (Phila Pa 1976). 2022-11-1

[2]
Sovateltide Mediated Endothelin B Receptors Agonism and Curbing Neurological Disorders.

Int J Mol Sci. 2022-3-15

[3]
Safety and Efficacy of Sovateltide (IRL-1620) in a Multicenter Randomized Controlled Clinical Trial in Patients with Acute Cerebral Ischemic Stroke.

CNS Drugs. 2021-1

[4]
Spinal Cord Injury: Pathophysiology, Multimolecular Interactions, and Underlying Recovery Mechanisms.

Int J Mol Sci. 2020-10-13

[5]
Sovateltide (IRL-1620) activates neuronal differentiation and prevents mitochondrial dysfunction in adult mammalian brains following stroke.

Sci Rep. 2020-7-29

[6]
Anti-apoptotic activity of ET receptor agonist, IRL-1620, protects neural cells in rats with cerebral ischemia.

Sci Rep. 2019-7-18

[7]
Endothelin-1 Decreases Excitability of the Dorsal Root Ganglion Neurons via ET Receptor.

Mol Neurobiol. 2017-6-16

[8]
Rat models of spinal cord injury: from pathology to potential therapies.

Dis Model Mech. 2016-10-1

[9]
Effects of ganglioside G(M1) and erythropoietin on spinal cord lesions in rats: functional and histological evaluations.

Clinics (Sao Paulo). 2016-7

[10]
Analysis of equivalent parameters of two spinal cord injury devices: the New York University impactor versus the Infinite Horizon impactor.

Spine J. 2016-11

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