Iron overload in the motor cortex induces neuronal ferroptosis following spinal cord injury

Feng, Zhanchun; Min, Lingxia; Chen, Hui; Deng, Weiwei; Tan, Mingliang; Liu, Hongliang; Hou, Jingming

doi:10.1016/j.redox.2021.101984

Cited by 106 publications

(75 citation statements)

References 50 publications

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“…Similarly, we speculate that the sharply changed pH value, oxidation level and ion metabolism disturbance after IR may account for the early emergence of iron transport disruption and the occurrence of ferroptosis. As the overloaded Fe 2+ facilitates the production of ROS via Fenton reaction and the generation of lipid hydroperoxides, which impair cellular structures such as membranes [ 29 ], it is conceivable that the immediate increase of iron metabolism after retinal IR is the initiation factor for ferroptosis, and the following lipid dysbolism secondary to iron accumulation may further enlarge the death area and prolong the death course (Fig. 7 ).…”

Section: Discussionmentioning

confidence: 99%

Inhibiting multiple forms of cell death optimizes ganglion cells survival after retinal ischemia reperfusion injury

Qin

et al. 2022

Cell Death Dis

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Progressive retinal ganglion cells (RGCs) death that triggered by retinal ischemia reperfusion (IR), leads to irreversible visual impairment and blindness, but our knowledge of post-IR neuronal death and related mechanisms is limited. In this study, we first demonstrated that apart from necroptosis, which occurs before apoptosis, ferroptosis, which is characterized by iron deposition and lipid peroxidation, is involved in the whole course of retinal IR in mice. Correspondingly, all three types of RGCs death were found in retina samples from human glaucoma donors. Further, inhibitors of apoptosis, necroptosis, and ferroptosis (z-VAD-FMK, Necrostatin-1, and Ferrostatin-1, respectively) all exhibited marked RGC protection against IR both in mice and primary cultured RGCs, with Ferrostatin-1 conferring the best therapeutic effect, suggesting ferroptosis plays a more prominent role in the process of RGC death. We also found that activated microglia, Müller cells, immune responses, and intracellular reactive oxygen species accumulation following IR were significantly mitigated after each inhibitor treatment, albeit to varying degrees. Moreover, Ferrostatin-1 in combination with z-VAD-FMK and Necrostatin-1 prevented IR-induced RGC death better than any inhibitor alone. These findings stand to advance our knowledge of the post-IR RGC death cascade and guide future therapy for RGC protection.

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Section: Discussionmentioning

confidence: 99%

Inhibiting multiple forms of cell death optimizes ganglion cells survival after retinal ischemia reperfusion injury

Qin

et al. 2022

Cell Death Dis

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“…Graphene quantum dots trigger ferroptosis in microglia through mitochondrial oxidative stress [37]. Based on these results, Feng et al concluded that microglial activation after SCI caused ferroptosis of motor neurons and impaired the recovery of motor function [38]. Evidence suggests that ferroptosis is associated with multiple neurologic conditions, making it an increasingly important mechanism of CNS degeneration with microglial activation or polarization [39][40][41].…”

Section: Discussionmentioning

confidence: 99%

Wild Bitter Melon Extract Abrogates Hypoxia-Induced Cell Death via the Regulation of Ferroptosis, ER Stress, and Apoptosis in Microglial BV2 Cells

Lin

Hsieh

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Microglial cells are well-known phagocytic cells that are resistant to the central nervous system (CNS) and play an important role in the maintenance of CNS homeostasis. Activated microglial cells induce neuroinflammation under hypoxia and typically cause neuronal damage in CNS diseases. In this study, we propose that wild bitter melon extract (WBM) has a protective effect on hypoxia-induced cell death via regulation of ferroptosis, ER stress, and apoptosis. The results demonstrated that hypoxia caused microglial BV-2 the accumulation of lipid ROS, ferroptosis, ER stress, and apoptosis. In this study, we investigated the pharmacological effects of WBM on BV-2 cells following hypoxia-induced cell death. The results indicated that WBM reversed hypoxia-downregulated antiferroptotic molecules Gpx4 and SLC7A11, as well as upregulated the ER stress markers CHOP and Bip. Moreover, WBM alleviated hypoxia-induced apoptosis via the regulation of cleaved-caspase 3, Bax, and Bcl-2. Our results suggest that WBM may be a good candidate for preventing CNS disorders in the future.

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“…These structurally damaged mitochondria were dysfunctional and unable to produce sufficient ATP for neurons to maintain normal physiological activities. A previous study using a rat model of SCI demonstrated ROS accumulation, aberrant mitochondria, and neuronal loss in the motor cortex [ 56 ]. In addition, a recent publication showed that restore mitochondrial function by some therapeutic approaches could delay the onset and slow the progression of Alzheimer's disease [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Hippocampal Mitochondrial Abnormalities Induced the Dendritic Complexity Reduction and Cognitive Decline in a Rat Model of Spinal Cord Injury

Wen³

et al. 2022

Oxidative Medicine and Cellular Longevity

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Spinal cord injury (SCI) is a progressive neurodegenerative disease in addition to a traumatic event. Cognitive dysfunction following SCI has been widely reported in patients and animal models. However, the neuroanatomical changes affecting cognitive function after SCI, as well as the mechanisms behind these changes, have so far remained elusive. Herein, we found that SCI accelerates oxidative stress damage of hippocampal neuronal mitochondria. Then, for the first time, we presented a three-dimensional morphological atlas of rat hippocampal neurons generated using a fluorescence Micro-Optical Sectioning Tomography system, a method that accurately identifies the spatial localization of neurons and trace neurites. We showed that the number of dendritic branches and dendritic length was decreased in late stage of SCI. Western blot and transmission electron microscopy analyses also showed a decrease in synaptic communication. In addition, a battery of behavioral tests in these animals revealed hippocampal based cognitive dysfunction, which could be attributed to changes in the dendritic complexity of hippocampal neurons. Taken together, these results suggested that mitochondrial abnormalities in hippocampal neurons induced the dendritic complexity reduction and cognitive decline following SCI. Our study highlights the neuroanatomical basis and importance of mitochondria in brain degeneration following SCI, which might contribute to propose new therapeutic strategies.

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Iron overload in the motor cortex induces neuronal ferroptosis following spinal cord injury

Cited by 106 publications

References 50 publications

Inhibiting multiple forms of cell death optimizes ganglion cells survival after retinal ischemia reperfusion injury

Inhibiting multiple forms of cell death optimizes ganglion cells survival after retinal ischemia reperfusion injury

Wild Bitter Melon Extract Abrogates Hypoxia-Induced Cell Death via the Regulation of Ferroptosis, ER Stress, and Apoptosis in Microglial BV2 Cells

Hippocampal Mitochondrial Abnormalities Induced the Dendritic Complexity Reduction and Cognitive Decline in a Rat Model of Spinal Cord Injury

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