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Life Sciences › Neuroscience › Developmental Neuroscience
Iron overload contributes to general anaesthesia-induced neurotoxicity and cognitive deficits
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Conflicts of Interest
Identified Weaknesses
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Paper Summary
Paperzilla title
Knock Out the Iron, Knock Out the Brain Drain: Anesthesia's Iron Grip on Cognition
General anesthesia (GA) disrupts iron homeostasis in the brain, leading to iron overload and triggering ferroptosis, a form of iron-dependent cell death. Chelating excess iron with deferiprone or blocking iron uptake through DMT1 can prevent neuronal damage and improve cognitive outcomes after GA exposure, indicating potential therapeutic strategies for GA-induced cognitive deficits.
Possible Conflicts of Interest
None identified
Identified Weaknesses
High Ketamine Concentration In Vitro
The in vitro experiments used a high concentration of ketamine (10 μM), which may not reflect clinically relevant doses and could lead to exaggerated effects not seen in vivo.
Indirect Measurement of Iron
The study relies heavily on pharmacological interventions (DFP and DMT1i) to support the role of iron, but lacks direct measurement of iron levels in specific brain regions or cell types.
Non-Specific Cognitive Tests
The cognitive tests used (MWM and fear conditioning) are not specific to iron overload and may be affected by other factors related to GA.
Lack of Long-Term Follow-up
The study does not investigate the long-term effects of GA-induced iron overload on cognitive function beyond a few days post-exposure.
Incomplete Mechanistic Understanding
The mechanisms linking GA, iron overload, and ferroptosis are not fully elucidated, and alternative pathways or contributing factors may exist.
Rating Explanation
This study presents compelling evidence for the role of iron overload in GA-induced neurotoxicity and cognitive deficits, using a combination of in vitro and in vivo models. The pharmacological interventions with DFP and DMT1i further strengthen the link between iron and GA's effects. However, some limitations, such as the high ketamine concentration used in vitro and the lack of long-term follow-up, prevent a higher rating.
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File Information
Original Title:
Iron overload contributes to general anaesthesia-induced neurotoxicity and cognitive deficits
File Name:
s12974-020-01777-6.pdf
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File Size:
3.11 MB
Uploaded:
July 14, 2025 at 11:18 AM
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