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犬退行性脊髓病的强化神经康复和同种异体干细胞移植

Intensive neurorehabilitation and allogeneic stem cells transplantation in canine degenerative myelopathy.

作者信息

Gouveia Débora, Correia Jéssica, Cardoso Ana, Carvalho Carla, Oliveira Ana Catarina, Almeida António, Gamboa Óscar, Ribeiro Lénio, Branquinho Mariana, Sousa Ana, Lopes Bruna, Sousa Patrícia, Moreira Alícia, Coelho André, Rêma Alexandra, Alvites Rui, Ferreira António, Maurício Ana Colette, Martins Ângela

机构信息

Arrábida Veterinary Hospital, Arrábida Animal Rehabilitation Center, Setubal, Portugal.

Superior School of Health, Protection and Animal Welfare, Polytechnic Institute of Lusophony, Lisboa, Portugal.

出版信息

Front Vet Sci. 2023 Jul 13;10:1192744. doi: 10.3389/fvets.2023.1192744. eCollection 2023.

Abstract

INTRODUCTION

Degenerative myelopathy (DM) is a neurodegenerative spinal cord disease with upper motor neurons, with progressive and chronic clinical signs, similar to amyotrophic lateral sclerosis (ALS). DM has a complex etiology mainly associated with SOD1 gene mutation and its toxic role, with no specific treatment. Daily intensive rehabilitation showed survival time near 8 months but most animals are euthanized 6-12 months after clinical signs onset.

METHODS

This prospective controlled blinded cohort clinical study aims to evaluate the neural regeneration response ability of DM dogs subjected to an intensive neurorehabilitation protocol with mesenchymal stem cells (MSCs) transplantation. In total, 13 non-ambulatory (OFS 6 or 8) dogs with homozygous genotype DM/DM and diagnosed by exclusion were included. All were allocated to the intensive neurorehabilitation with MSCs protocol (INSCP) group ( = 8) or to the ambulatory rehabilitation protocol (ARP) group ( = 5), which differ in regard to training intensity, modalities frequency, and MSCs transplantation. The INSCP group was hospitalized for 1 month (T0 to T1), followed by MSCs transplantation (T1) and a second month (T2), whereas the ARP group was under ambulatory treatment for the same 2 months.

RESULTS

Survival mean time of total population was 375 days, with 438 days for the INSCP group and 274 for the ARP group, with a marked difference on the Kaplan-Meier survival analysis. When comparing the literature's results, there was also a clear difference in the one-sample -test ( = 0.013) with an increase in time of approximately 70%. OFS classifications between groups at each time point were significantly different ( = 0.008) by the one-way ANOVA and the independent sample -test.

DISCUSSION

This INSCP showed to be safe, feasible, and a possibility for a long progression of DM dogs with quality of life and functional improvement. This study should be continued.

摘要

引言

退行性脊髓病(DM)是一种以上运动神经元受累的神经退行性脊髓疾病,具有进行性和慢性临床症状,类似于肌萎缩侧索硬化症(ALS)。DM病因复杂,主要与超氧化物歧化酶1(SOD1)基因突变及其毒性作用有关,尚无特异性治疗方法。每日强化康复治疗显示存活时间接近8个月,但大多数动物在出现临床症状后6 - 12个月实施安乐死。

方法

本前瞻性对照盲法队列临床研究旨在评估接受间充质干细胞(MSC)移植强化神经康复方案的DM犬的神经再生反应能力。总共纳入13只非行走型(OFS 6或8)、基因型为纯合子DM/DM且经排除诊断的犬。所有犬被分配到接受MSC强化神经康复方案(INSCP)组(n = 8)或行走康复方案(ARP)组(n = 5),两组在训练强度、训练方式频率和MSC移植方面存在差异。INSCP组住院1个月(T0至T1),随后进行MSC移植(T1)并再住院1个月(T2),而ARP组在相同的2个月内接受门诊治疗。

结果

总体人群的平均存活时间为375天。INSCP组为438天,ARP组为274天,在Kaplan - Meier生存分析中有显著差异。与文献结果比较时,单样本t检验也有明显差异(P = 0.013),时间增加约70%。各时间点两组间的OFS分类经单因素方差分析和独立样本t检验有显著差异(P = 0.008)。

讨论

该INSCP方案显示对DM犬安全、可行,并且有可能实现其长期病情进展延缓,同时改善生活质量和功能。本研究应继续开展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f90/10374290/79a20d2e8ae3/fvets-10-1192744-g0001.jpg

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