Ischemia stroke is one of the leading causes of death and disability worldwide. Owing to the limited delivery efficiency to the brain caused by the blood-brain barrier (BBB) and off-target effects of systemic treatment, it is crucial to develop an drug delivery system to improve the therapeutic effect in ischemic stroke. Briefly, we report a multifunctional hydrogel delivery system for the co-delivery of reactive oxygen species (ROS)-responsive nanoparticles loaded with atorvastatin calcium (DSPE-se-se-PEG@AC NPs) and β-nerve growth factor (NGF), which is expected to remodel pathological microenvironment for improving cerebral ischemia injury. The results exhibited the multifunctional hydrogel scavenged oxygen-glucose deprivation (OGD)-induced free radical, rescued the mitochondrial function, and maintained the survival and function of neurons, hence reducing neuronal apoptosis and neuroinflammation, consequently relieving ischemia injury in hippocampal neurons cell line (HT22). In the rat ischemia stroke model, the hydrogel significantly minified cerebral infarction by regulating inflammatory response, saving apoptotic neurons, and promoting angiogenesis and neurogenesis. Besides, the hydrogel distinctly improved the rats' neurological deficits after cerebral ischemia injury over the long-term observation. In conclusion, the hydrogel platform has demonstrated promising therapeutic effects in both and studies, indicating its potential as a new and effective therapy.

中文翻译：

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多功能注射水凝胶重塑脑病理微环境减轻脑缺血损伤


缺血性中风是全世界死亡和残疾的主要原因之一。由于血脑屏障（BBB）导致大脑的递送效率有限以及全身治疗的脱靶效应，开发药物递送系统以提高缺血性中风的治疗效果至关重要。简而言之，我们报告了一种多功能水凝胶递送系统，用于共同递送负载阿托伐他汀钙（DSPE-se-se-PEG@AC NPs）和β-神经生长因子（NGF）的活性氧（ROS）响应纳米颗粒，有望重塑病理微环境，改善脑缺血损伤。结果表明，多功能水凝胶可以清除氧糖剥夺（OGD）诱导的自由基，挽救线粒体功能，维持神经元的存活和功能，从而减少神经元凋亡和神经炎症，从而减轻海马神经元细胞系的缺血损伤。 HT22）。在大鼠缺血性中风模型中，水凝胶通过调节炎症反应、拯救凋亡神经元、促进血管生成和神经发生，显着缩小脑梗塞。此外，经过长期观察，水凝胶明显改善了大鼠脑缺血损伤后的神经功能缺损。总之，水凝胶平台在研究中表现出了有希望的治疗效果，表明其作为一种新的有效疗法的潜力。