Ma Yuanhao, Liu Yu, Guo Jianqiang, Chen Zhongjun, Zhao Zongren, Zheng Jinyu
Department of Neurosurgery, Affiliated Huaian Hospital of Xuzhou Medical University, Huaian, China.
Department of Neurosurgery, Huzhou Central Hospital, Huzhou, China.
Front Neurosci. 2024 Aug 7;18:1450072. doi: 10.3389/fnins.2024.1450072. eCollection 2024.
Traumatic brain injury (TBI) causes neuronal cell damage and dysfunction. According to previous studies, daphnetin (Dap) has a protective effect in neurological injury. However, the bioavailability of daphnetin is not high. The purpose of this study was to determine whether administering daphnetin directly into the site of injury via a hydrogel drug carrier could improve its therapeutic impact.
Tripolycerol monostearates / daphnetin (TM/Dap) hydrogels were prepared and characterised using water bath heating, scanning electron microscopy (SEM) and small animal imaging techniques. The TBI model was established using the Feeney free fall impact method. Using the Morris water maze test, the mNSS neurological deficit rating scale, haematoxylin-eosin staining, and liver and kidney function tests, the therapeutic benefit of TM/Dap and its toxic side effects were assessed. The therapeutic effects of TM/Dap were further investigated using wet and dry gravimetric methods, Evans blue staining, protein immunoblotting, immunofluorescence staining techniques and ELISA.
The efficacy of the TM/Dap hydrogel in gradually releasing daphnetin in the context of traumatic brain damage was shown by both and tests. Behavioral experiments showed that the learning and spatial memory abilities of TM/Dap hydrogel treated mice were significantly improved in the water maze experiment. And TM/Dap hydrogel has high biosafety for organisms. The results of the therapeutic mechanism of action showed that TM/Dap hydrogel showed more significant efficacy in reducing the neuroinflammatory response caused by TNF-α, IL-6 and other factors, as well as promoting the recovery of post-traumatic neurological function.
The use of hydrogel as a drug carrier for daphnetin showed more significant efficacy in reducing neuroinflammatory response, protecting nerve tissue and promoting post-traumatic neurological recovery compared with traditional drug delivery methods.
创伤性脑损伤（TBI）会导致神经元细胞损伤和功能障碍。根据以往研究，瑞香素（Dap）对神经损伤具有保护作用。然而，瑞香素的生物利用度不高。本研究的目的是确定通过水凝胶药物载体将瑞香素直接注射到损伤部位是否能提高其治疗效果。
采用水浴加热、扫描电子显微镜（SEM）和小动物成像技术制备并表征三聚甘油单硬脂酸酯/瑞香素（TM/Dap）水凝胶。采用Feeney自由落体撞击法建立TBI模型。通过莫里斯水迷宫试验、mNSS神经功能缺损评分量表、苏木精-伊红染色以及肝肾功能检测，评估TM/Dap的治疗效果及其毒副作用。采用干湿重量法、伊文思蓝染色、蛋白质免疫印迹、免疫荧光染色技术和酶联免疫吸附测定（ELISA）进一步研究TM/Dap的治疗效果。
体内和体外试验均表明TM/Dap水凝胶在创伤性脑损伤情况下能逐渐释放瑞香素。行为学实验表明，在水迷宫实验中，经TM/Dap水凝胶处理的小鼠的学习和空间记忆能力显著提高。并且TM/Dap水凝胶对生物体具有较高的生物安全性。作用机制的治疗结果表明，TM/Dap水凝胶在减轻由肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）等因子引起的神经炎症反应以及促进创伤后神经功能恢复方面显示出更显著的疗效。
与传统给药方法相比，使用水凝胶作为瑞香素的药物载体在减轻神经炎症反应、保护神经组织以及促进创伤后神经恢复方面显示出更显著的疗效。
