作者: |
Xiang Xu1#, Zhihui Han2#, Dong Li1,3#, Xingshun Xu4,5, Yaobo Liu5, Cong Cao5, Jin Tao5,6, Jian Cheng6, John H Zhang7, Liang Cheng2* & Gang Chen1* |
单位: |
1Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. 2Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China. 3Department of Neurosurgery, Lianyungang TCM Hospital, Affiliated to Nanjing University of Chinese Medicine, Liangyungang 222000, China. 4Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. 5Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou 215123, China. 6Department of Physiology and Neurobiology, Medical College of Soochow University, Suzhou 215123, China. 7Department of Physiology and Pharmacology, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA. |
摘要: |
Inflammatory responses and neuronal ferroptosis, which are associated with abnormal accumulation of reactive oxygen species (ROS), exert crucial damaging effects on the brain after intracerebral hemorrhage (ICH). In this study, minocycline (MC)‐loaded cerium oxide nanoparticles (CeO2‐MC) are constructed for combined ICH treatment. Ultra-small CeO2(≈5 nm) synthesized via a high-temperature approach exhibits powerful free‐radical scavenging and iron‐chelating abilities. In vitro experiments demonstrated that CeO2‐MC effectively attenuated the ROS levels in mouse microglial cells and neurons following oxyhemoglobin stimulation. In addition, CeO2‐MC exhibits iron chelation properties and stabilizes the mitochondrial membrane potential, thereby promoting anti-inflammatory responses and preventing neuronal ferroptosis. In an intracerebral hemorrhage (ICH) mouse model, CeO2-MC exhibited robust free radical scavenging capabilities and demonstrated the ability to preserve mitochondrial morphology and function, mitigate brain edema, and maintain blood-brain barrier integrity by inhibiting neuroinflammation and ferroptosis. Neurobehavioral tests demonstrated that CeO2‐MC significantly ameliorated spatial learning ability and sensorimotor function after ICH. Consequently, a general strategy using CeO2nanoparticles to augment the therapeutic efficacy of MC highlights a new perspective for the in‐depth treatment of ICH. |