Tsai May-Jywan, Liou Dann-Ying, Fay Li-Yu, Huang Shih-Ling, Huang Wen-Cheng, Chern Chang-Ming, Tsai Shen-Kou, Cheng Henrich, Huang Shiang-Suo
Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
Division of Neural Regeneration and Repair, Neurological Institute, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
Int J Mol Sci. 2025 Apr 17;26(8):3821. doi: 10.3390/ijms26083821.
Ischemic stroke leads to cerebral ionic imbalance, increases acidosis, oxidative stress and release of glutamate and inflammatory mediators. Removing solute or stimulants from the ischemic core may block cell-damaging events and confer neuroprotection. In this study, we developed a minimally invasive therapeutic microdialysis (tMD) method, choosing to include serum albumin in the buffer because it is a multifunctional protein with osmotic properties. Aiming at the ischemic core, continuous perfusion of buffer supplemented with osmotic agents removes mediators of inflammation/cell damage/death from the lesion. This tMD treatment significantly removed the glutamate and zinc ions from the core, thereby reducing infarct volumes and affording high-grade neurobehavioral protection against ischemic stroke. The tMD treatment effectively protected neurons and reduced microglial activation. Furthermore, this tMD approach extended the therapeutic window to protect beyond 6 h after stroke onset. These findings support the potential clinical feasibility of applying tMD to patients with ischemic stroke, potentially without adverse effects.
缺血性中风会导致脑离子失衡，增加酸中毒、氧化应激以及谷氨酸和炎症介质的释放。从缺血核心区清除溶质或刺激物可能会阻断细胞损伤事件并提供神经保护作用。在本研究中，我们开发了一种微创治疗性微透析（tMD）方法，选择在缓冲液中加入血清白蛋白，因为它是一种具有渗透特性的多功能蛋白质。针对缺血核心区，持续灌注添加渗透剂的缓冲液可从病变部位清除炎症/细胞损伤/死亡的介质。这种tMD治疗显著从核心区清除了谷氨酸和锌离子，从而减小了梗死体积，并为缺血性中风提供了高度的神经行为保护。tMD治疗有效保护了神经元并减少了小胶质细胞的激活。此外，这种tMD方法延长了治疗窗口，可在中风发作后6小时以上提供保护。这些发现支持了将tMD应用于缺血性中风患者的潜在临床可行性，且可能无不良影响。
