Shao Qi, Chen Simin, Zheng Yuxiao, Xu Wenxiu, Chen Jiahui, Shao Wei, Wang Qingguo, Li Changxiang, Wang Xueqian
College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Qingdao Key Laboratory of Neurorehabilitation, University of Health and Rehabilitation Sciences, Qingdao, Shandong Province, China.
Neural Regen Res. 2026 Mar 1;21(3):1000-1012. doi: 10.4103/NRR.NRR-D-24-01109. Epub 2025 Mar 25.
Chronic cerebral hypoperfusion can lead to neuronal necrosis, trigger inflammatory responses, promote white matter damage, and ultimately result in cognitive impairment. Consequently, chronic cerebral hypoperfusion is an important factor influencing the onset and progression of vascular dementia. The myelin sheath is a critical component of white matter, and damage and repair of the white matter are closely linked to myelin sheath integrity. This article reviews the role of microglia in vascular dementia, focusing on their effects on myelin sheaths and the potential therapeutic implications. The findings suggest that ischemia and hypoxia cause disruption of the blood-brain barrier and activate microglia, which may worsen blood-brain barrier damage through the release of matrix-degrading enzymes. Microglia-mediated metabolic reprogramming is recognized as an important driver of inflammation. Damage to the blood-brain barrier and subsequent inflammation can lead to myelin injury and accelerate the progression of vascular dementia. Early activation of microglia is a protective response that contributes to the maintenance of blood-brain barrier integrity through sensing, debris-clearing, and defensive mechanisms. However, prolonged activation can trigger a shift in microglia toward the pro-inflammatory M1 phenotype, resulting in myelin damage and cognitive impairment. Triggering receptor expressed on myeloid cells 2 and triggering receptor expressed on myeloid cells 1 have been identified as potential biomarkers for vascular dementia, as both are closely linked to cognitive decline. Although effective clinical treatments for myelin damage in the central nervous system are currently lacking, researchers are actively working to develop targeted therapies. Several drugs, including nimodipine, dopaminergic agents, simvastatin, biotin, and quetiapine, have been evaluated for clinical use in treating microglial and myelin damage. Future research will face challenges in developing targeted therapeutic strategies for vascular dementia, requiring further investigation into the timing, duration, and specific mechanisms of microglial activation, as well as the exploration of new drug combinations and additional therapeutic targets.
慢性脑灌注不足可导致神经元坏死，引发炎症反应，促进白质损伤，并最终导致认知障碍。因此，慢性脑灌注不足是影响血管性痴呆发病和进展的重要因素。髓鞘是白质的关键组成部分，白质的损伤和修复与髓鞘完整性密切相关。本文综述了小胶质细胞在血管性痴呆中的作用，重点关注它们对髓鞘的影响以及潜在的治疗意义。研究结果表明，缺血缺氧会导致血脑屏障破坏并激活小胶质细胞，小胶质细胞可能通过释放基质降解酶使血脑屏障损伤恶化。小胶质细胞介导的代谢重编程被认为是炎症的重要驱动因素。血脑屏障损伤及随后的炎症可导致髓鞘损伤并加速血管性痴呆的进展。小胶质细胞的早期激活是一种保护性反应，通过感知、清除碎片和防御机制有助于维持血脑屏障的完整性。然而，长时间激活可促使小胶质细胞向促炎M1表型转变，导致髓鞘损伤和认知障碍。髓系细胞触发受体2和髓系细胞触发受体1已被确定为血管性痴呆的潜在生物标志物，因为它们都与认知功能下降密切相关。尽管目前缺乏针对中枢神经系统髓鞘损伤的有效临床治疗方法，但研究人员正在积极致力于开发靶向治疗方法。几种药物，包括尼莫地平、多巴胺能药物、辛伐他汀、生物素和喹硫平，已被评估用于治疗小胶质细胞和髓鞘损伤的临床应用。未来的研究在为血管性痴呆开发靶向治疗策略方面将面临挑战，需要进一步研究小胶质细胞激活的时间、持续时间和具体机制，以及探索新的药物组合和其他治疗靶点。
