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Association of Microbleeds on Susceptibility-Weighted Imaging with Ferroptosis and Prognosis in Rabbits with Spinal
Xing-Zhen Liu1, Bo-Cheng Wang2, Kang-Ping Shen1
1Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011 Shanghai, China.
Background:
Susceptibility-weighted imaging (SWI) is a common imaging technique used to identify cerebral microbleeds. Given that spinal cord injury (SCI) often creates an environment that favors ferroptosis, a type of cell death driven by iron, this study aimed to explore the relationship between microbleeds on SWI and ferroptosis, and explore the effect of deferoxamine on SCI.
Methods:
Thirty-six rabbits were divided into three groups: sham, SCI, and SCI with deferoxamine (DFO, a ferroptosis inhibitor) treatment (SCI+DFO). Following 48 hours of SCI modeling, the rabbits underwent magnetic resonance imaging (MRI) and SWI examinations. Ferroptosis markers and spinal cord tissue morphology were examined, and the modified Tarlov's score was used to assess neurological function.
Results:
SWI analysis revealed that rabbits in the SCI group exhibited lower signal intensities and larger microbleed areas compared to the those in the SCI+DFO group (p < 0.05). The SCI+DFO group demonstrated significantly decreased iron and malondialdehyde (MDA) levels, coupled with increased glutathione (GSH) and glutathione peroxidase 4 (GPX4) levels, along with attenuated ferroptosis (p < 0.05). This group also displayed greater Neuronal Nuclei (NeuN) expression, Tarlov's scores, and neurological recovery rates (all p < 0.05). A significant positive correlation was found between the microbleed area and iron content (r = 0.59, p = 0.04), MDA (r = 0.75, p = 0.01), and mitochondrial damage (r = 0.90, p < 0.01). Conversely, a negative correlation was established between the microbleed area and GPX4 levels (r = -0.87, p < 0.01), as well as neurological function recovery (r = -0.62, p = 0.03).
Conclusion:
The extent of microbleeds on SWI following SCI is closely correlated with ferroptosis, and the inhibition of ferroptosis could improve neurologic function. These findings suggest that the area of microbleeds on SWI could potentially serve as a predictive marker for ferroptosis in spinal cord injury.
Insights
Spinal cord injury (SCI) microbleeds identified by susceptibility-weighted imaging (SWI) correlate with ferroptosis. Inhibiting ferroptosis with deferoxamine (DFO) improved neurological function and reduced microbleeds in rabbits.
Area of Science:
- Neuroscience
- Biomedical Imaging
- Cellular Biology
Background:
- Susceptibility-weighted imaging (SWI) is crucial for detecting cerebral microbleeds.
- Spinal cord injury (SCI) can induce an iron-driven cell death pathway known as ferroptosis.
- This study investigates the link between SCI-induced microbleeds and ferroptosis.
Purpose of the Study:
- To explore the relationship between microbleeds on SWI and ferroptosis in SCI.
- To evaluate the therapeutic effect of deferoxamine (DFO), a ferroptosis inhibitor, on SCI.
- To determine if SWI microbleed area can predict ferroptosis in SCI.
Main Methods:
- Thirty-six rabbits were divided into sham, SCI, and SCI with DFO treatment groups.
- Magnetic resonance imaging (MRI) and SWI were performed 48 hours post-SCI.
- Ferroptosis markers, spinal cord morphology, and neurological function (Tarlov's score) were assessed.
Main Results:
- SCI rabbits showed increased microbleed area and iron content compared to DFO-treated rabbits.
- DFO treatment attenuated ferroptosis, decreasing iron and MDA, and increasing GSH and GPX4 levels.
- Microbleed area positively correlated with iron, MDA, and mitochondrial damage, and negatively with GPX4 and neurological recovery.
Conclusions:
- Microbleed extent on SWI after SCI is strongly associated with ferroptosis.
- Inhibiting ferroptosis with DFO improves neurological function and recovery in SCI.
- SWI-assessed microbleed area may serve as a predictive biomarker for ferroptosis in spinal cord injury.

