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Published on: May 4, 2020
Exploring the link between iron dysregulation, ferroptosis, and cognitive dysfunction in intracerebral hemorrhage
Liang Hao1, Aobo Zhang2, Dongsheng Lv3
1Department of Neurosurgery, The Third Hospital of Shijiazhuang, Shijiazhuang, China.
Insights
Iron metabolism disturbances and ferroptosis are linked to cognitive impairment in patients with intracerebral hemorrhage (ICH). Elevated iron in cerebrospinal fluid (CSF) also correlates with reduced cognitive function in ICH survivors.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Intracerebral hemorrhage (ICH) is a severe neurological condition.
- Cognitive impairment is a common sequela of ICH.
- The role of iron metabolism and ferroptosis in ICH-related cognitive decline requires further elucidation.
Purpose of the Study:
- To investigate the association between iron metabolism, ferroptosis, cerebrospinal fluid (CSF) iron levels, and cognitive impairment in ICH patients.
- To compare these markers between ICH patients and a control group with external brain injury.
Main Methods:
- Included 80 ICH patients and 36 controls.
- Utilized magnetic resonance imaging (MRI) to assess ICH.
- Measured protein expressions of ferroptosis markers (GPX4, FSP1) and iron metabolism proteins (transferrin, ferritin, ferritransporters).
- Assessed CSF iron ion levels and malondialdehyde (MDA).
- Evaluated cognitive function using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales.
Main Results:
- ICH patients exhibited elevated GPX4, FSP1, transferrin, ferritin, ferritransporter expressions, and CSF iron ion levels compared to controls.
- Malondialdehyde (MDA) levels were higher in the ICH group.
- ICH patients showed significantly lower MMSE and MoCA scores, indicating cognitive impairment.
- Cognitive scores negatively correlated with iron metabolism markers, ferroptosis markers, and CSF iron levels.
Conclusions:
- Disturbances in iron metabolism and ferroptosis are closely associated with cognitive impairment in ICH.
- Elevated CSF iron ion levels in ICH patients correlate with cognitive deficits.
- These findings highlight potential therapeutic targets for mitigating cognitive decline post-ICH.
Objective:
The present study aimed to investigate the association between iron metabolism, ferroptosis, cerebrospinal fluid (CSF) iron ion levels, and cognitive impairment in patients with intracerebral hemorrhage (ICH).
Methods:
A total of 80 ICH patients treated at the Department of Neurology and Emergency Department of our hospital were included in the study. Additionally, 36 patients with external brain injury (without intracerebral hemorrhage) were recruited as a control group. Magnetic resonance imaging (MRI) was used to assess the location and extent of intracerebral bleeding in the observation group (ICH group).
Results:
The protein expressions of GPX4 and FSP1 were found to be elevated in the ICH group (P < 0.05). Similarly, the expressions of iron metabolism-related proteins, including transferrin, ferritin, and ferritransporters, were significantly higher in the brain tissue of the ICH group (P < 0.05). Malondialdehyde (MDA) levels were also elevated in the ICH group (MDA: 4.45 ± 0.47 vs. 3.31 ± 0.35 nmol/ml). Furthermore, the level of iron ions in the CSF was higher in the ICH group (P < 0.05). Cognitive assessments showed that MMSE and MoCA scores in the ICH group were significantly lower than those in the control group (P < 0.05), indicating more severe cognitive impairment in the observation group. Moreover, MMSE and MoCA scores were negatively correlated with iron metabolism-related proteins (transferrin, ferritin, and ferritransporters), ferroptosis markers (GPX4 and FSP1), and CSF iron ion levels (P < 0.05).
Conclusion:
Disturbances in iron metabolism, the occurrence of ferroptosis, and increased CSF iron ion levels in ICH patients appear to be closely associated with cognitive impairment.
