Guo Wenliang, Wu Yinteng, Zhao Shijian, Xu Jianwen
Department of Rehabilitation Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Department of Orthopedic and Trauma Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Front Endocrinol (Lausanne). 2025 Oct 17;16:1627414. doi: 10.3389/fendo.2025.1627414. eCollection 2025.
Spinal cord injury (SCI), a debilitating neurological disorder with complex pathophysiology, involves primary mechanical trauma followed by multifactorial cascades of secondary inflammation, oxidative stress, and apoptosis. Hormones have emerged as a research focus in SCI therapeutics due to their neuroprotective properties. As pivotal regulators of cellular signaling, hormones exhibit dual roles in either exacerbating or mitigating secondary damage. This review synthesizes three decades of research, highlighting that hormones such as corticosteroids, melatonin, and estrogen demonstrate significant therapeutic potential in animal models and clinical studies, though controversies persist regarding their efficacy and safety profiles. Key findings include: (1) Glucocorticoids, exemplified by methylprednisolone (MP), suppress inflammation and reduce tissue damage but face skepticism over long-term benefits, with high-dose regimens correlating with significant adverse effects such as gastrointestinal bleeding, hyperglycemia, and metabolic complications; (2) Melatonin exerts multi-target neuroprotection by modulating autophagy, inhibiting apoptosis, and suppressing inflammasome activation; (3) Sex hormones (e.g., testosterone, progesterone) improve functional recovery through metabolic balance regulation and neural regeneration, while estrogen enhances angiogenesis and motor function via the synergistic involvement of multiple receptor-mediated genomic (ERα/ERβ) and non-genomic (GPER) signaling pathways. The non-genomic actions rapidly activate kinase cascades, such as PI3K/Akt-CREB and ERK, which in turn regulate both immediate cellular functions and gene expression profiles, contributing to the overall neuroprotective effects; (4) Combinatorial therapies (e.g., MP with neurotrophic factors) and novel delivery systems (e.g., nanoparticle-based drug carriers) represent promising strategies to optimize therapeutic outcomes. These advances elucidate the multidimensional mechanisms of hormonal interventions while revealing critical challenges, including dose-dependent adverse effects, antagonistic effects in polypharmacy, and unresolved long-term safety concerns. Overall, hormonal therapies for SCI present a "dual-edged sword" of efficacy versus risks, necessitating future innovations in precision regulation and mechanistic exploration to bridge translational gaps.
脊髓损伤（SCI）是一种具有复杂病理生理学的使人衰弱的神经系统疾病，包括原发性机械性创伤，随后是继发炎症、氧化应激和细胞凋亡的多因素级联反应。由于其神经保护特性，激素已成为SCI治疗学的研究重点。作为细胞信号传导的关键调节因子，激素在加重或减轻继发性损伤方面具有双重作用。本综述综合了三十年的研究，强调皮质类固醇、褪黑素和雌激素等激素在动物模型和临床研究中显示出显著的治疗潜力，尽管关于它们的疗效和安全性仍存在争议。主要发现包括：（1）以甲基强的松龙（MP）为例的糖皮质激素可抑制炎症并减少组织损伤，但长期益处受到质疑，高剂量方案与胃肠道出血、高血糖和代谢并发症等重大不良反应相关；（2）褪黑素通过调节自噬、抑制细胞凋亡和抑制炎性小体激活发挥多靶点神经保护作用；（3）性激素（如睾酮、孕酮）通过调节代谢平衡和神经再生改善功能恢复，而雌激素通过多种受体介导的基因组（ERα/ERβ）和非基因组（GPER）信号通路的协同作用增强血管生成和运动功能。非基因组作用迅速激活激酶级联反应，如PI3K/Akt-CREB和ERK，进而调节即时细胞功能和基因表达谱，有助于整体神经保护作用；（4）联合疗法（如MP与神经营养因子）和新型递送系统（如基于纳米颗粒的药物载体）是优化治疗效果的有前景的策略。这些进展阐明了激素干预的多维度机制，同时揭示了关键挑战，包括剂量依赖性不良反应、多药联用中的拮抗作用以及未解决的长期安全性问题。总体而言，SCI的激素疗法是一把疗效与风险并存的“双刃剑”，需要未来在精准调节和机制探索方面进行创新，以弥合转化差距。
