Daoyong Li1, He Tian2, Xian Li1, Liang Mao3, Xiaoguang Zhao4, Jiaquan Lin1, Sen Lin1, Chang Xu1, Yuanye Liu1, Yue Guo5, Xifan Mei6. 1. Department of Orthopedics, The First Affifiliated Hospital of Jinzhou Medical University, Jinzhou, China. 2. Department of Histology and Embryology, Jinzhou Medical University, Jinzhou, China. 3. Department of Oncology, The First Affifiliated Hospital of Jinzhou Medical University, Jinzhou, China. 4. Department of Emergency, The First Affifiliated Hospital of Jinzhou Medical University, Jinzhou, China. 5. Department of Postgraduate, The First Affifiliated Hospital of Jinzhou Medical University, Jinzhou, China. 6. Department of Orthopedics, The First Affifiliated Hospital of Jinzhou Medical University, Jinzhou, China. Electronic address: meixifan@jzmu.edu.cn.
Abstract
AIMS: To study the specific therapeutic effect of zinc on spinal cord injury (SCI) and its specific protective mechanism. MAIN METHODS: The effects of zinc ions on neuronal cells were examined in a mouse SCI model and in vitro. In vivo, neurological function was assessed by Basso Mouse Scaleat (BMS) at 1, 3, 5, 7, 10, 14, 21, and 28 days after spinal cord injury. The number of neurons and histomorphology were observed by nissl staining and hematoxylin-eosin staining (HE). The chromatin and mitochondrial structure of neurons were detected by transmission electron microscopy (TEM). The expression of nuclear factor erythroid 2 related factor 2 (Nrf2)-related antioxidant protein and NLRP3 inflammation-related protein were detected in vivo and in vitro by western blot (WB) and immunofluorescence (IF), respectively. KEY FINDINGS: Zinc treatment promoted motor function recovery on days 3, 5, 7, 14, 21 and 28 after SCI. In addition, zinc reduces the mitochondrial void rate in spinal neuronal cells and promotes neuronal recovery. At the same time, zinc reduced the levels of reactive oxygen species (ROS) and malondialdehyde in spinal cord tissue after SCI, while increasing superoxide dismutase activity and glutathione peroxidase production. Zinc treatment resulted in up-regulation of Nrf2/Ho-1 levels and down-regulation of nlrp3 inflammation-associated protein expression in vitro and in vivo. SIGNIFICANCE: Zinc has a protective effect on spinal cord injury by inhibiting oxidative damage and nlrp3 inflammation. Potential mechanisms may include activation of the Nrf 2/Ho-1 pathway to inhibit nlrp3 inflammation following spinal cord injury. Zinc has the potential to treat SCI.
AIMS: To study the specific therapeutic effect of zinc on spinal cord injury (SCI) and its specific protective mechanism. MAIN METHODS: The effects of zinc ions on neuronal cells were examined in a mouseSCI model and in vitro. In vivo, neurological function was assessed by Basso Mouse Scaleat (BMS) at 1, 3, 5, 7, 10, 14, 21, and 28 days after spinal cord injury. The number of neurons and histomorphology were observed by nissl staining and hematoxylin-eosin staining (HE). The chromatin and mitochondrial structure of neurons were detected by transmission electron microscopy (TEM). The expression of nuclear factor erythroid 2 related factor 2 (Nrf2)-related antioxidant protein and NLRP3inflammation-related protein were detected in vivo and in vitro by western blot (WB) and immunofluorescence (IF), respectively. KEY FINDINGS: Zinc treatment promoted motor function recovery on days 3, 5, 7, 14, 21 and 28 after SCI. In addition, zinc reduces the mitochondrial void rate in spinal neuronal cells and promotes neuronal recovery. At the same time, zinc reduced the levels of reactive oxygen species (ROS) and malondialdehyde in spinal cord tissue after SCI, while increasing superoxide dismutase activity and glutathione peroxidase production. Zinc treatment resulted in up-regulation of Nrf2/Ho-1 levels and down-regulation of nlrp3inflammation-associated protein expression in vitro and in vivo. SIGNIFICANCE: Zinc has a protective effect on spinal cord injury by inhibiting oxidative damage and nlrp3inflammation. Potential mechanisms may include activation of the Nrf 2/Ho-1 pathway to inhibit nlrp3inflammation following spinal cord injury. Zinc has the potential to treat SCI.
Authors: Anna Lucia Fedullo; Mario Ciccotti; Paolo Giannotta; Federica Alviti; Marco Bernardi; Anna Raguzzini; Elisabetta Toti; Tommaso Sciarra; Ilaria Peluso Journal: Oxid Med Cell Longev Date: 2021-02-27 Impact factor: 6.543