{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:02:14Z","timestamp":1790276534295,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100016867","name":"ZOLL Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016867","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Cardiac arrest (CA) is a major health burden with brain damage being a significant contributor to mortality. We found lysophosphatidylcholine (LPC), including a species containing docosahexaenoic acid (LPC\u2010DHA), was significantly decreased in plasma post\u2010CA, supplementation of which significantly improved neurological outcomes. The aim of this study is to understand the protective role of LPC\u2010DHA supplementation on the brain post\u2010CA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We first evaluated associations between the plasma level of LPC\u2010DHA and neurological injury and outcomes of human patients with CA. We then utilized a rat CA model and cell cultures to investigate therapeutic and mechanistic aspects of plasma LPC\u2010DHA supplementation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that decreased plasma LPC\u2010DHA was strongly associated with neurological outcomes and disappearance of the difference between gray and white matter in the brain after CA in human patients. In rats, the decreased plasma LPC\u2010DHA was associated with decreased levels of brain LPC\u2010DHA after CA, and supplementing plasma LPC\u2010DHA normalized brain levels of LPC\u2010DHA and alleviated neuronal cell death, activation of astrocytes, and expression of various inflammatory and mitochondrial dynamics genes. We also observed deceased severity of metabolic alterations with LPC\u2010DHA supplementation using untargeted metabolomics analysis. Furthermore, LPC treatment showed a similar protective effect for neurons and astrocytes in mixed primary brain cell cultures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>The observed neuroprotection accompanied with normalized brain LPC\u2010DHA level by plasma supplementation implicate the importance of preventing the decrease of brain LPC\u2010DHA post\u2010CA for attenuating brain injury. Furthermore, the data supports the causative role of decreased plasma LPC\u2010DHA for brain damage after CA. 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