Dataset Information

Ferrostatin-1 facilitated neurological functional rehabilitation of spinal cord injury mice by inhibiting ferroptosis.

ABSTRACT:

Background

To seek the potential therapy for spinal cord injury, Ferrostatin-1, the first ferroptosis inhibitor, was administrated in spinal cord injury mice to identify the therapeutic effect.

Methods

Spinal cord injury model was established by a modified Allen's method. Then, ferrostatin-1 was administrated by intraspinal injection. Cortical evoked motor potential and BMS were indicated to assess the neurological function rehabilitation. H&E, Nissl's staining, NeuN, and GFAP immunofluorescence were used to identify the histological manifestation on the mice with the injured spinal cord. Spinosin, a selective small molecule activator of the Nrf2/HO-1 signaling pathway, was administrated to verify the underlying mechanism of ferrostatin-1.

Results

Ferrostatin-1 promoted the rehabilitation of cortical evoked motor potential and BMS scores, synchronized with improvement in the histological manifestation of neuron survival and scar formation. Spinosin disturbed the benefits of ferrostatin-1 administration on histological and neurobehavioral manifestation by deranging the Nrf2/HO-1 signaling pathway.

Conclusions

Ferrostatin-1 improved the rehabilitation of spinal cord injury mice by regulating ferroptosis through the Nrf2/HO-1 signaling pathway.

SUBMITTER: Zhou Z

PROVIDER: S-EPMC10494332 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Ferrostatin-1 facilitated neurological functional rehabilitation of spinal cord injury mice by inhibiting ferroptosis.

Zhou Zhenhai Z Luo Hao H Yu Honggui H Liu Zhiming Z Zhong Junlong J Xiong Jiachao J Cao Kai K

European journal of medical research 20230911 1

<h4>Background</h4>To seek the potential therapy for spinal cord injury, Ferrostatin-1, the first ferroptosis inhibitor, was administrated in spinal cord injury mice to identify the therapeutic effect.<h4>Methods</h4>Spinal cord injury model was established by a modified Allen's method. Then, ferrostatin-1 was administrated by intraspinal injection. Cortical evoked motor potential and BMS were indicated to assess the neurological function rehabilitation. H&E, Nissl's staining, NeuN, and GFAP imm ...[more]

PMID: 37697399

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Project description:Chronic compressive spinal cord injury in compressive cervical myelopathy conditions can lead to rapid neurological deterioration in the early phase, followed by partial self-recovery, and ultimately an equilibrium state of neurological dysfunction. Ferroptosis is a crucial pathological process in many neurodegenerative diseases; however, its role in chronic compressive spinal cord injury remains unclear. In this study, we established a chronic compressive spinal cord injury rat model, which displayed its most severe behavioral and electrophysiological dysfunction at 4 weeks and partial recovery at 8 weeks after compression. Bulk RNA sequencing data identified enriched functional pathways, including ferroptosis, presynapse, and postsynaptic membrane activity at both 4 and 8 weeks following chronic compressive spinal cord injury. Transmission electron microscopy and malondialdehyde quantification assay confirmed that ferroptosis activity peaked at 4 weeks and was attenuated at 8 weeks after chronic compression. Ferroptosis activity was negatively correlated with behavioral score. Immunofluorescence, quantitative polymerase chain reaction, and western blotting showed that expression of the anti-ferroptosis molecules, glutathione peroxidase 4 (GPX4) and MAF BZIP transcription factor G (MafG), in neurons was suppressed at 4 weeks and upregulated at 8 weeks following spinal cord compression. There was a positive correlation between the expression of these two molecules, suggesting that they may work together to contribute to functional recovery following chronic compressive spinal cord injury. In conclusion, our study determined the genome-wide expression profile and ferroptosis activity of a consistently compressed spinal cord at different time points. The results showed that anti-ferroptosis genes, specifically GPX4 and MafG, may be involved in spontaneous neurological recovery at 8 weeks of chronic compressive spinal cord injury. These findings contribute to a better understanding of the mechanisms underlying chronic compressive spinal cord injury and may help identify new therapeutic targets for compressive cervical myelopathy.

Dataset Information

Ferrostatin-1 facilitated neurological functional rehabilitation of spinal cord injury mice by inhibiting ferroptosis.

Background

Methods

Results

Conclusions

Publications

Ferrostatin-1 facilitated neurological functional rehabilitation of spinal cord injury mice by inhibiting ferroptosis.

Similar Datasets

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