Xue Hang, Ding Zixuan, Chen Xiaoyan, Yang Xu, Jia Yufei, Zhao Ping, Wu Ziyi
Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Mol Neurobiol. 2025 Apr;62(4):4866-4880. doi: 10.1007/s12035-024-04564-z. Epub 2024 Nov 4.
Neonatal hypoxic-ischemic brain injury (HIBI) can lead to white matter damage, which significantly contributes to cognitive dysfunction, emotional disorders, and sensorimotor impairments. Although dexmedetomidine enhances neurobehavioral outcomes, its impact on oligodendrocyte genesis and myelination following hypoxic-ischemic events, as well as the underlying mechanisms, remain poorly understood. Dexmedetomidine was administered 15 min post-HIBI. We assessed neurobehavioral deficits using various tests: surface righting, negative geotaxis, forelimb grip strength, cliff avoidance, sensory reflexes, novel object recognition, T-maze, and three-chamber social interaction. We also investigated the relationship between myelination and neurobehavioral outcomes. Measurements included oligodendrocyte precursor cell (OPC) proliferation and survival 24 h post-injury, early myelination, and oligodendrocyte differentiation by postnatal day 14. Furthermore, we evaluated microglial activation towards the M2 phenotype and the extent of neuroinflammation during the acute phase. Dexmedetomidine significantly ameliorated long-term neurological deficits caused by HIBI. Pearson linear regression analysis revealed a strong correlation between long-term neurological outcomes and myelin maturity. The treatment notably mitigated the long-term deterioration of myelin formation and maturation following HIBI. This protective effect was primarily due to enhanced OPC proliferation and survival post-HIBI during the acute phase and, to a lesser extent, to the modulation of microglial activity towards the M2 phenotype and a reduction in neuroinflammation. Dexmedetomidine offers substantial protection against long-term neurobehavioral disabilities induced by HIBI, primarily by revitalizing the impaired survival and maturation of oligodendrocyte progenitor cells and promoting myelination.
新生儿缺氧缺血性脑损伤（HIBI）可导致白质损伤，这在很大程度上导致认知功能障碍、情绪障碍和感觉运动障碍。尽管右美托咪定可改善神经行为结果，但其对缺氧缺血事件后少突胶质细胞生成和髓鞘形成的影响以及潜在机制仍知之甚少。在HIBI后15分钟给予右美托咪定。我们使用各种测试评估神经行为缺陷：表面翻正、负趋地性、前肢握力、悬崖回避、感觉反射、新物体识别、T迷宫和三室社交互动。我们还研究了髓鞘形成与神经行为结果之间的关系。测量包括损伤后24小时少突胶质前体细胞（OPC）的增殖和存活、早期髓鞘形成以及出生后第14天少突胶质细胞的分化。此外，我们评估了急性期小胶质细胞向M2表型的激活以及神经炎症的程度。右美托咪定显著改善了HIBI引起的长期神经功能缺损。Pearson线性回归分析显示长期神经功能结果与髓鞘成熟度之间存在强相关性。该治疗显著减轻了HIBI后髓鞘形成和成熟的长期恶化。这种保护作用主要是由于急性期HIBI后OPC增殖和存活增强，以及在较小程度上由于小胶质细胞活性向M2表型的调节和神经炎症的减少。右美托咪定对HIBI诱导的长期神经行为残疾提供了实质性保护，主要是通过恢复受损的少突胶质前体细胞的存活和成熟并促进髓鞘形成。
