Traumatic brain injury-related ferroptosis: current perspectives

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• Traumatic brain injury (TBI) is a major cause of death and disability.
• Secondary injury mechanisms, including ferroptosis, worsen neuronal damage after TBI.
• Ferroptosis is an iron-dependent cell death characterized by lipid peroxidation.

Purpose of the Study:

• To review current evidence on ferroptosis in TBI.
• To highlight ferroptosis pathways and their intersection with other cellular processes.
• To discuss therapeutic strategies targeting ferroptosis for TBI.

Main Methods:

• Literature review synthesizing current evidence on ferroptosis in TBI.
• Analysis of ferroptosis core pathways: iron metabolism, lipid peroxidation, and glutathione depletion.
• Examination of TBI-associated ferroptosis markers and therapeutic interventions.

Main Results:

• Ferroptosis involves iron dysregulation, lipid peroxidation (ACSL4/LPCAT3), and glutathione depletion (System Xc-/GSH/GPX4).
• Ferroptosis exacerbates neuronal death by interacting with mitochondrial dysfunction, ER stress, and neuroinflammation.
• The hippocampus shows increased ferroptosis markers post-TBI; various agents demonstrate neuroprotection.

Conclusions:

• Targeting ferroptosis pathways offers a potential therapeutic strategy for TBI.
• Further research is needed to address gaps in understanding ferroptosis crosstalk and clinical translation.
• Optimizing drug delivery and validating biomarkers are crucial for clinical application.