College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, 30 Puzhu South Road, Nanjing, 211816, People's Republic of China.
Institute of Biological Chinese Medicine, Beijing Yichuang Institute of Biotechnology Industry, Beijing, 100023, China.
Mol Neurobiol. 2024 Jan;61(1):434-449. doi: 10.1007/s12035-023-03588-1. Epub 2023 Aug 25.
Ischemic stroke is a heterogeneous brain injury with complex pathophysiology and it is also a time sensitive neurological injury disease. At present, the treatment options for ischemic stroke are still limited. 6S-5-methyltetrahydrofolate-calcium (MTHF-Ca) is the calcium salt of the predominant form of dietary folate in circulation. MTHF-Ca has potential neuroprotective effect on neurocytes, but whether it can be used for ischemic stroke treatment remains unknown. We established zebrafish ischemic stroke model through photothrombotic method to evaluate the protective effect of MTHF-Ca on the ischemic brain injury of zebrafish. We demonstrated that MTHF-Ca reduced the brain damage by reducing motor dysfunction and neurobehavioral defects of zebrafish with telencephalon infarction injury. MTHF-Ca counteracted oxidative damages after Tel injury by increasing the activities of GSH-Px and SOD and decreasing the content of MDA. RNA-seq and RT-qPCR results showed that MTHF-Ca played a neuroprotective role by alleviating neuroinflammation, inhibiting blood coagulation, and neuronal apoptosis processes. Overall, we have demonstrated that MTHF-Ca has neuroprotective effect in ischemic stroke and can be used as a potential treatment for ischemic stroke.
缺血性脑卒中是一种异质性的脑损伤，具有复杂的病理生理学机制，也是一种时间敏感的神经损伤性疾病。目前，缺血性脑卒中的治疗选择仍然有限。6S-5-甲基四氢叶酸钙（MTHF-Ca）是循环中膳食叶酸的主要形式的钙盐。MTHF-Ca 对神经细胞具有潜在的神经保护作用，但它是否可用于缺血性脑卒中的治疗尚不清楚。我们通过光血栓形成法建立了斑马鱼缺血性脑卒中模型，以评估 MTHF-Ca 对斑马鱼缺血性脑损伤的保护作用。我们证明 MTHF-Ca 通过减少患有大脑前脑损伤的斑马鱼的运动功能障碍和神经行为缺陷来减轻脑损伤。MTHF-Ca 通过增加 GSH-Px 和 SOD 的活性并降低 MDA 的含量来抵抗 Tel 损伤后的氧化损伤。RNA-seq 和 RT-qPCR 结果表明，MTHF-Ca 通过减轻神经炎症、抑制血液凝固和神经元凋亡过程发挥神经保护作用。总的来说，我们已经证明 MTHF-Ca 在缺血性脑卒中中有神经保护作用，可作为缺血性脑卒中的潜在治疗方法。
