Synergistic effects of neural stem cells and ibrutinib on neural tissue repair and functional recovery in a contusion mouse model of spinal cord injury

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters Pub Date : 2025-02-05 DOI:10.1016/j.neulet.2025.138149

Somayyeh Torabi , Zahra Zeraatpisheh , Seyed Hadi Anjamrooz , Amir Ghanbari , Syed Shadab Raza , Hadi Aligholi , Hassan Azari

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Abstract

Modulating the immune response following spinal cord injury (SCI) is vital for establishing a conducive microenvironment that supports the survival and engraftment of transplanted neural stem/progenitor cells (NSPCs). Building on our prior findings of ibrutinib’s immunotherapeutic potential in acute SCI, this study investigates the impact of ibrutinib administration on NSPC survival, fate and their potential synergistic effects on tissue repair and motor function in a contusive mouse model of SCI.

Green fluorescence expressing NSPCs were transplanted into the lesion site with or without concurrent ibrutinib administration. Over four weeks, comprehensive assessments included behavioral evaluations, lesion volume measurements, and analyses of the survival, fate, and migration patterns of the transplanted cells. The results revealed that ibrutinib and NSPCs individually reduced lesion volume and improved motor functions. However, their combination significantly accelerated and enhanced motor recovery. Furthermore, ibrutinib improved cell viability, increasing markers for oligodendrocyte and neuroblast while concurrently diminishing the expression of astrocyte marker glial fibrillary acidic protein (GFAP).

In conclusion, the combined utilization of ibrutinib and NSPC transplantation presents a promising strategy for enhancing tissue repair, promoting functional recovery, and positively modulating cell behaviors in the context of SCI.

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神经干细胞和伊布替尼对脊髓损伤挫伤小鼠模型中神经组织修复和功能恢复的协同作用

调节脊髓损伤（SCI）后的免疫反应对于建立有利于移植神经干/祖细胞（NSPCs）存活和移植的微环境至关重要。基于我们之前发现的依鲁替尼在急性脊髓损伤中的免疫治疗潜力，本研究探讨了依鲁替尼给药对脊髓损伤小鼠模型中NSPC存活、命运的影响，以及它们对组织修复和运动功能的潜在协同作用。同时给予或不给予依鲁替尼，将表达绿色荧光的NSPCs移植到病变部位。在四周的时间里，综合评估包括行为评估、病变体积测量、移植细胞的存活、命运和迁移模式分析。结果显示，伊鲁替尼和NSPCs分别减少病变体积和改善运动功能。然而，它们的结合显著地加速和增强了运动恢复。此外，伊鲁替尼提高了细胞活力，增加了少突胶质细胞和神经母细胞的标记物，同时降低了星形胶质细胞标记物胶质纤维酸性蛋白（GFAP）的表达。综上所述，在脊髓损伤的情况下，联合应用依鲁替尼和NSPC移植是一种很有前景的策略，可以增强组织修复，促进功能恢复，并积极调节细胞行为。

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

Neuroscience Letters 医学-神经科学

CiteScore

5.20

自引率

0.00%

发文量

408

审稿时长

50 days

期刊介绍： Neuroscience Letters is devoted to the rapid publication of short, high-quality papers of interest to the broad community of neuroscientists. Only papers which will make a significant addition to the literature in the field will be published. Papers in all areas of neuroscience - molecular, cellular, developmental, systems, behavioral and cognitive, as well as computational - will be considered for publication. Submission of laboratory investigations that shed light on disease mechanisms is encouraged. Special Issues, edited by Guest Editors to cover new and rapidly-moving areas, will include invited mini-reviews. Occasional mini-reviews in especially timely areas will be considered for publication, without invitation, outside of Special Issues; these un-solicited mini-reviews can be submitted without invitation but must be of very high quality. Clinical studies will also be published if they provide new information about organization or actions of the nervous system, or provide new insights into the neurobiology of disease. NSL does not publish case reports.