Preserving Brain LPC‐DHA by Plasma Supplementation Attenuates Brain Injury after Cardiac Arrest

Abstract

Objective 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‐DHA), was significantly decreased in plasma post‐CA, supplementation of which significantly improved neurological outcomes. The aim of this study is to understand the protective role of LPC‐DHA supplementation on the brain post‐CA. Methods We first evaluated associations between the plasma level of LPC‐DHA 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‐DHA supplementation. Results We found that decreased plasma LPC‐DHA 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‐DHA was associated with decreased levels of brain LPC‐DHA after CA, and supplementing plasma LPC‐DHA normalized brain levels of LPC‐DHA 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‐DHA supplementation using untargeted metabolomics analysis. Furthermore, LPC treatment showed a similar protective effect for neurons and astrocytes in mixed primary brain cell cultures. Interpretation The observed neuroprotection accompanied with normalized brain LPC‐DHA level by plasma supplementation implicate the importance of preventing the decrease of brain LPC‐DHA post‐CA for attenuating brain injury. Furthermore, the data supports the causative role of decreased plasma LPC‐DHA for brain damage after CA. ANN NEUROL 2022;91:389–403

The Role of Phospholipid Alterations in Mitochondrial and Brain Dysfunction after Cardiac Arrest

“…Additionally, defects in nuclear genes can lead to phospholipid metabolism disorders, particularly in mitochondrial diseases like Barth syndrome and dilated cardiomyopathy [14,15]. Recent investigations, including our own study, suggest that alterations in phospholipids, particularly within mitochondria, may significantly contribute to brain dysfunction following cardiac arrest [16][17][18][19]. This review aims to explore the potential involvement of mitochondrial phospholipids in neural damage subsequent to cardiac arrest, with the objective of enhancing our comprehension of the pathophysiological mechanisms driving post-cardiac arrest brain injury.…”

Neuroprotective Approaches for Brain Injury After Cardiac Arrest: Current Trends and Prospective Avenues

“…Lysophosphatidylcholine containing docosahexaenoic acid (LPC-DHA) is a form of omega-3 fatty acid, which is significantly decreased in post-CA plasma in rats and humans [ 63 ]. In a 10-minute asphyxia rat CA model, IV injection of 6 mg/kg LPC-DHA (0.5 mL) 1 minute after ROSC over 1 minute significantly improved neurological functions as assessed by neuronal reflex test and motor coordination test at 72 hours after ROSC [ 64 ]. Supplementation of LPC-DHA normalized brain levels of LPC-DHA and alleviated neuronal cell death, activation of astrocytes, and expression of various inflammatory and mitochondrial dynamics genes.…”

The role of omega-3 polyunsaturated fatty acids in the intensive care unit

“…It is proposed that low availability of LPC-DHA may play a causative role for brain injury after cardiac arrest [58 ▪ ]. In rats, supplementing with LPC-DHA normalized brain levels of LPC-DHA and alleviated neuronal cell death, activation of astrocytes, and expression of various inflammatory and mitochondrial dynamics genes [59]. Another study observed that acute brain injury (intracerebral hemorrhage) triggers the synthesis of neuroprotectin D1, a DHA-derived SPM: neuroprotectin D1 levels were higher in patients with better 90-day outcome [60].…”