脊髓损伤后小胶质细胞-血管相互作用：调控机制与治疗进展
Microglia-vascular interactions after spinal cord injury: regulatory mechanisms and therapeutic advances.
摘要(中文译文)
脊髓损伤（SCI）后的修复过程涉及神经免疫系统与血管系统之间复杂的相互作用，其中小胶质细胞与血管的相互作用日益被认为是可能影响继发性损伤进展和神经再生的重要调控界面。本综述阐述了血管生成在SCI中的双重作用：功能成熟的新生血管可促进血供恢复、提供神经营养支持并为轴突再生提供导向线索；相反，结构异常且高通透性的血管可加剧血-脊髓屏障（BSCB）破坏、放大炎症反应并维持局部缺氧，从而阻碍功能恢复。作为中枢神经系统（CNS）的主要驻留免疫细胞，小胶质细胞通过动态的、情境依赖的功能状态显著影响血管生成的启动、延伸和成熟，这些状态通常在M1/M2框架内进行操作性讨论。反之，血管损伤、屏障渗漏、缺氧相关信号及内皮源性介质可重塑小胶质细胞的活化和功能，从而建立双向相互作用网络。针对该轴的治疗策略正从非选择性地促进血管生成转向多模式和分阶段的干预，包括调节小胶质细胞状态、外泌体介导的生物活性分子递送、功能化生物材料支架、通路导向的药理学方法以及物理康复策略的整合。这些方法在临床前模型中已显示出令人鼓舞的效果，包括改善血管成熟、减轻炎症损伤和改善神经功能结局。未来研究应结合单细胞多组学、空间分辨图谱分析、成像和智能生物材料，以阐明不同细胞亚群的时空动态，强化临床前证据基础，并支持小胶质细胞-血管轴调控用于SCI修复的更严谨的转化研究。
Abstract
The repair process following spinal cord injury (SCI) involves intricate crosstalk between neuroimmune and vascular systems, with microglia-vascular interactions increasingly recognized as an important regulatory interface that may shape both secondary injury progression and neural regeneration. This review delineates the dual role of angiogenesis in SCI: functionally mature neovessels can facilitate restoration of blood supply, provide neurotrophic support, and offer guidance cues for axonal regrowth; in contrast, structurally abnormal and hyperpermeable vessels can exacerbate blood-spinal cord barrier (BSCB) disruption, amplify inflammatory responses, and perpetuate local hypoxia, thereby impeding functional recovery. As the primary resident immune cells of the central nervous system (CNS), microglia substantially influence the initiation, extension, and maturation of angiogenesis through dynamic, context-dependent functional states that are often operationally discussed within the M1/M2 framework. Conversely, vascular injury, barrier leakage, hypoxia-associated signaling, and endothelial-derived mediators can reshape microglial activation and function, establishing a bidirectional interaction network. Therapeutic strategies targeting this axis are shifting from indiscriminate angiogenesis promotion toward multimodal and stage-aware interventions, including modulation of microglial states, exosome-mediated delivery of bioactive molecules, functionalized biomaterial scaffolds, pathway-directed pharmacological approaches, and integration of physical rehabilitation strategies. These approaches have shown encouraging effects in preclinical models, including improved vascular maturation, reduced inflammatory injury, and better neurological outcomes. Future studies should combine single-cell multi-omics, spatially resolved profiling, imaging, and smart biomaterials to clarify the spatiotemporal dynamics of distinct cellular subpopulations, strengthen the preclinical evidence base, and support more rigorous translation of microglia-vascular axis regulation for SCI repair.
如何引用
AMA
Yulin Zhao, Weiyun Wang, Shihao Li, Manglai Li, Wenwu Zhang, Tan Lu, et al. Microglia-vascular interactions after spinal cord injury: regulatory mechanisms and therapeutic advances.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1856481.
APA
Yulin Zhao, Weiyun Wang, Shihao Li, Manglai Li, Wenwu Zhang, Tan Lu, et al (2026). Microglia-vascular interactions after spinal cord injury: regulatory mechanisms and therapeutic advances.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1856481
GB/T 7714
Yulin Zhao, Weiyun Wang, Shihao Li, Manglai Li, Wenwu Zhang, Tan Lu, et al. Microglia-vascular interactions after spinal cord injury: regulatory mechanisms and therapeutic advances.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1856481.
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