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Preserving Brain LPC-DHA by Plasma Supplementation Attenuates Brain Injury after Cardiac Arrest
Mitsuaki Nishikimi1,2, Muhammad Shoaib1,3, Rishabh C Choudhary1
1Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Insights
Lysophosphatidylcholine with docosahexaenoic acid (LPC-DHA) supplementation improved neurological outcomes after cardiac arrest (CA). Restoring LPC-DHA levels in the brain mitigated neuronal damage and inflammation, highlighting its neuroprotective potential.
Area of Science:
- Neuroscience
- Biochemistry
- Cardiology
Background:
- Cardiac arrest (CA) poses a significant health risk, with brain damage contributing substantially to mortality.
- Lysophosphatidylcholine (LPC), particularly LPC with docosahexaenoic acid (LPC-DHA), is found to be decreased in plasma after CA.
Purpose of the Study:
- To investigate the neuroprotective role of LPC-DHA supplementation on the brain following cardiac arrest.
- To understand the therapeutic and mechanistic aspects of plasma LPC-DHA supplementation post-CA.
Main Methods:
- Evaluation of associations between plasma LPC-DHA levels and neurological outcomes in human CA patients.
- Utilizing a rat CA model and primary brain cell cultures to assess the effects of LPC-DHA supplementation.
- Employing untargeted metabolomics to analyze metabolic alterations.
Main Results:
- Decreased plasma LPC-DHA correlated with poorer neurological outcomes and altered brain matter in human patients.
- In a rat CA model, plasma LPC-DHA supplementation normalized brain LPC-DHA levels, reducing neuronal death, astrocyte activation, and inflammatory/mitochondrial gene expression.
- LPC treatment demonstrated neuroprotective effects in primary brain cell cultures.
- Metabolomic analysis revealed reduced severity of metabolic alterations with LPC-DHA supplementation.
Conclusions:
- Plasma LPC-DHA supplementation offers neuroprotection post-CA by normalizing brain LPC-DHA levels.
- Preventing the decrease of brain LPC-DHA is crucial for attenuating CA-induced brain injury.
- The study supports a causative role for decreased plasma LPC-DHA in post-CA brain damage.
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.
