Transcriptomic Remodeling of the Spinal Cord-Injured Bladder and Its Modulation by Inosine Treatment

Neurogenic detrusor overactivity (NDO) is a frequent complication of spinal cord injury (SCI), often accompanied by profound structural and functional changes in the bladder. While inosine has previously been shown to improve bladder function in SCI models, its molecular effects on the bladder remain largely unexplored. In this study, we performed transcriptomic profiling of bladder tissues from SCI rats treated with inosine or vehicle. Bladder compartments were microdissected into detrusor and mucosa to capture compartment-specific changes. SCI induced widespread transcriptional alterations in both compartments, with inosine treatment partially restoring gene expression patterns toward those observed in non-injured controls. Unsupervised clustering and principal component analyses confirmed distinct transcriptional profiles associated with injury and treatment. Notably, inosine influenced a set of genes consistently altered by SCI, suggesting a protective or regulatory role at the molecular level. These findings reveal a compartment-specific transcriptomic response to spinal cord injury and provide insight into the mechanisms by which inosine may exert its therapeutic effects on the injured bladder.神经源性逼尿肌过度活动（Neurogenic detrusor overactivity, NDO）是脊髓损伤（spinal cord injury, SCI）的常见并发症，常伴随膀胱出现显著的结构与功能改变。此前已有研究证实，肌苷（inosine）可改善脊髓损伤模型的膀胱功能，但其对膀胱的分子层面调控作用仍未得到充分探索。本研究对经肌苷或赋形剂处理的脊髓损伤大鼠膀胱组织开展了转录组谱分析。研究人员将膀胱组织通过显微解剖分离为逼尿肌层与黏膜层，以捕捉分区特异性的基因表达变化。脊髓损伤在两个组织分区中均诱导了广泛的转录组改变，而肌苷处理可部分将基因表达谱恢复至未损伤对照组的水平。无监督聚类与主成分分析证实，损伤与治疗分别对应了独特的转录组特征。值得注意的是，肌苷可调控一系列经脊髓损伤后发生一致性改变的基因，提示其在分子层面发挥保护或调控作用。本研究揭示了脊髓损伤引发的分区特异性转录组应答，并为解析肌苷对损伤膀胱的治疗作用机制提供了新的研究视角。