Hong Yongjae, Ko Geon, Jeon Yeong-Jae, Baek Hyeon-Man, Lee Juni, Lee Donghun, Park Jieun, Kim Jaehong, Chang Keun-A
Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences & Technology, Gachon University, Incheon 21999, Republic of Korea.
Department of Molecular Medicine, College of Medicine, Gachon University, Incheon 21999, Republic of Korea.
Cells. 2025 Jan 14;14(2):117. doi: 10.3390/cells14020117.
Stroke affects over 12 million people annually, leading to high mortality, long-term disability, and substantial healthcare costs. Although East Asian herbal medicines are widely used for stroke treatment, the pathways of operation they use remain poorly understood. Our study investigates the neuroprotective properties of (AM) in acute ischemic stroke using photothrombotic (PTB) and transient middle cerebral artery occlusion (tMCAO) mouse models, as well as an oxygen-glucose deprivation (OGD) model. Post-OGD treatment with AM improved cell viability in mouse neuroblastoma cells, likely by reducing reactive oxygen species (ROS). Mice received short-term (0-2 days) or long-term (0-27 days) AM treatment post-stroke. Infarct size was assessed using a 2,3,5-triphenyl tetrazolium chloride (TTC) staining procedure alongside magnetic resonance imaging (MRI). Neuroprotective metabolites including inositol (Ins), glycerophosphocholine+phosphocholine (GPc+ PCh), N-acetylaspartate+N-acetylaspartylglutamate (NAA+NAAG), creatine + phosphocreatine (Cr+PCr), and glutamine+glutamate (Glx) were analyzed via magnetic resonance spectroscopy (MRS). Gliosis was assessed using GFAP and Iba-1 immunohistochemical markers, while neurological deficits were quantified with modified neurological severity scores (mNSS). Motor and cognitive functions were assessed using cylinder, rotarod, and novel object recognition (NOR) tests. AM treatment significantly reduced ischemic damage and improved neurological outcomes in both acute and chronic stages of PTB and tMCAO models. Additionally, AM increased neuroprotective metabolites levels, reduced gliosis, and decreased oxidative stress, as evidenced by reduced inducible nitric oxide synthase (iNOS). These findings highlight the antioxidant properties of AM and its strong therapeutic potential for promoting recovery after ischemic stroke by alleviating neurological deficits, reducing gliosis, and mitigating oxidative stress.
中风每年影响超过1200万人，导致高死亡率、长期残疾和巨额医疗费用。尽管东亚草药被广泛用于中风治疗，但其作用途径仍知之甚少。我们的研究使用光血栓形成（PTB）和短暂性大脑中动脉闭塞（tMCAO）小鼠模型以及氧葡萄糖剥夺（OGD）模型，研究了[具体药物名称未给出]（AM）在急性缺血性中风中的神经保护特性。OGD后用AM治疗可提高小鼠神经母细胞瘤细胞的活力，可能是通过减少活性氧（ROS）实现的。中风后小鼠接受短期（0 - 2天）或长期（0 - 27天）的AM治疗。使用2,3,5 - 三苯基氯化四氮唑（TTC）染色程序并结合磁共振成像（MRI）评估梗死面积。通过磁共振波谱（MRS）分析神经保护代谢物，包括肌醇（Ins）、甘油磷酸胆碱+磷酸胆碱（GPc + PCh）、N - 乙酰天门冬氨酸+ N - 乙酰天门冬氨酰谷氨酸（NAA + NAAG）、肌酸+磷酸肌酸（Cr + PCr）和谷氨酰胺+谷氨酸（Glx）。使用胶质纤维酸性蛋白（GFAP）和离子钙结合衔接分子1（Iba - 1）免疫组化标记评估胶质增生，同时用改良神经功能缺损评分（mNSS）对神经功能缺损进行量化。使用圆柱体、转棒和新物体识别（NOR）测试评估运动和认知功能。AM治疗在PTB和tMCAO模型的急性和慢性阶段均显著减少了缺血损伤并改善了神经功能结局。此外，AM增加了神经保护代谢物水平，减少了胶质增生，并降低了氧化应激，这可通过诱导型一氧化氮合酶（iNOS）减少得到证明。这些发现突出了AM的抗氧化特性及其通过减轻神经功能缺损、减少胶质增生和减轻氧化应激来促进缺血性中风后恢复的强大治疗潜力。
