NIH R01 · 2025
Lipid Imaging in Traumatic Brain Injury by High Resolution GCIB-secondary Ion Mass Spectrometry
Traumatic brain injury (TBI) is a major cause of death and disability across all ages. Secondary injury mechanisms of phospholipid (PL) peroxidation and cell death are implied in the expansion of the damage caused by the primary insult. We discovered that a required step in necrotic cell death, ferroptosis, triggered by TBI is peroxidation of arachidonoyl-phosphatidylethanolamine (A-PE) catalyzed by enzymatic complex of 15-lipoxygenase (15LOX) with PE-binding protein (PEBP1). We also showed that acyl-CoA synthetase long-chain 4 (ACSL4), responsible for A-PE synthesis, is an essential positive ferroptosis regulator. However, two questions: 1) Which cell types undergo PE oxidation in…
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