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一种基于层粘连蛋白的犬慢性脊髓损伤治疗方法:一项纵向试验的可喜成果。

A laminin-based therapy for dogs with chronic spinal cord injury: promising results of a longitudinal trial.

作者信息

Chize Carolina de Miranda, Vivas Diego Gonzales, Menezes Karla, Freire Max Nascimento, Jiddu Rodrigo Ferreira Pinto, Graça-Souza Aurélio Vicente, de Souza-Leite Eliel, Louzada Paulo Roberto, Coelho-Sampaio Tatiana

机构信息

Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

Pathology Program, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Front Vet Sci. 2025 Aug 13;12:1592687. doi: 10.3389/fvets.2025.1592687. eCollection 2025.

Abstract

INTRODUCTION

Polylaminin, an improved form of the natural protein laminin, has been shown to promote axonal regeneration and functional recovery in animal models of acute spinal cord injury (SCI), and is safe and potentially beneficial in humans when administered within the first days after traumatic SCI. This study aimed to evaluate the effect of polylaminin in dogs with chronic SCI.

METHODS

We conducted a prospective, longitudinal study in six paraplegic dogs with severe chronic thoracolumbar SCI (T3-L3) caused by trauma ( = 2) or disc degeneration ( = 4). The study assessed whether gait scores, measured during an extended screening period (at least 4 months), would improve during the follow-up (6 months). Polylaminin was delivered intraspinally at a dose of 1 μg/kg, in combination with either glial-derived neurotrophic factor (GDNF; Group 1;  = 3) or chondroitinase ABC (Group 2;  = 3). Safety was assessed through neurological examinations, blood tests and monitoring of medical complications. Gait analysis was carried out using the Texas Spinal Cord Injury Scale (TSCIS) and the Open Field Scale (OFS), while a linear mixed model was used for statistical analysis. During the screening period, dogs received physiotherapy twice per week and had their gait scored periodically. The first six dogs whose scores had remained stable across three evaluations were enrolled. After owners provided informed consent, dogs were randomly allocated to either treatment group.

RESULTS

No neurological deterioration, serious clinical events or notable deviations in blood tests were observed. The TSCIS average baseline score increased from 2.2 to 3.2 (95% CI: 0.77-1.2;  < 0.001), while the OFS score increased from 1.5 to 3.1 (95% CI: 1.3-1.9;  < 0.001).

DISCUSSION

Although the present study could not discriminate between the benefits of the two treatments, our findings suggest that polylaminin, in combination with GDNF or chondroitinase ABC, is a safe and potentially effective treatment, which underscores the relevance of further studies to establish a new approach to improving gait function in dogs with chronic SCI.

摘要

引言

聚层粘连蛋白是天然蛋白层粘连蛋白的改良形式,已证实在急性脊髓损伤(SCI)动物模型中可促进轴突再生和功能恢复,并且在创伤性SCI后的头几天内给药时,对人类是安全且可能有益的。本研究旨在评估聚层粘连蛋白对慢性SCI犬的影响。

方法

我们对6只因创伤(n = 2)或椎间盘退变(n = 4)导致严重慢性胸腰椎SCI(T3-L3)的截瘫犬进行了一项前瞻性纵向研究。该研究评估了在延长的筛查期(至少4个月)测量的步态评分在随访期(6个月)是否会改善。聚层粘连蛋白以1μg/kg的剂量经脊髓内给药,与胶质细胞源性神经营养因子(GDNF;第1组;n = 3)或软骨素酶ABC(第2组;n = 3)联合使用。通过神经学检查、血液检查和医疗并发症监测评估安全性。使用德克萨斯脊髓损伤量表(TSCIS)和旷场量表(OFS)进行步态分析,同时使用线性混合模型进行统计分析。在筛查期,犬每周接受两次物理治疗,并定期对其步态进行评分。纳入前三评估中评分保持稳定的前6只犬。在主人提供知情同意后,将犬随机分配到任一治疗组。

结果

未观察到神经功能恶化、严重临床事件或血液检查中的显著偏差。TSCIS平均基线评分从2.2提高到3.2(95%CI:0.77-1.2;P<0.001),而OFS评分从1.5提高到3.1(95%CI:1.3-1.9;P<0.001)。

讨论

尽管本研究无法区分两种治疗方法的益处,但我们的研究结果表明,聚层粘连蛋白与GDNF或软骨素酶ABC联合使用是一种安全且可能有效的治疗方法,这突出了进一步研究以建立改善慢性SCI犬步态功能新方法的相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65fe/12380836/ed48ad7970cd/fvets-12-1592687-g001.jpg

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