Palmitic Acid Methyl Ester Inhibits Cardiac Arrest-induced Neuroinflammation and Mitochondrial Dysfunction

Overview

Journal Prostaglandins Leukot Essent Fatty Acids

Specialty Endocrinology

Date 2021 Jan 14

PMID 33445063

Citations 4

Authors

Celeste Yin-Chieh Wu

Alexandre Couto E Silva

Cristiane T Citadin

Garrett A Clemons

Christina H Acosta

Brianne A Knox

Mychal S Grames

Krista M Rodgers

Reggie Hui-Chao Lee

Hung Wen Lin

Affiliations

Soon will be listed here.

Abstract

We previously discovered that palmitic acid methyl ester (PAME) is a potent vasodilator released from the sympathetic ganglion with vasoactive properties. Post-treatment with PAME can enhance cortical cerebral blood flow and functional learning and memory, while inhibiting neuronal cell death in the CA1 region of the hippocampus under pathological conditions (i.e. cerebral ischemia). Since mechanisms underlying PAME-mediated neuroprotection remain unclear, we investigated the possible neuroprotective mechanisms of PAME after 6 min of asphyxial cardiac arrest (ACA, an animal model of global cerebral ischemia). Our results from capillary-based immunoassay (for the detection of proteins) and cytokine array suggest that PAME (0.02 mg/kg) can decrease neuroinflammatory markers, such as ionized calcium binding adaptor molecule 1 (Iba1, a specific marker for microglia/macrophage activation) and inflammatory cytokines after cardiopulmonary resuscitation. Additionally, the mitochondrial oxygen consumption rate (OCR) and respiratory function in the hippocampal slices were restored following ACA (via Seahorse XF24 Extracellular Flux Analyzer) suggesting that PAME can ameliorate mitochondrial dysfunction. Finally, hippocampal protein arginine methyltransferase 1 (PRMT1) and PRMT8 are enhanced in the presence of PAME to suggest a possible pathway of methylated fatty acids to modulate arginine-based enzymatic methylation. Altogether, our findings suggest that PAME can provide neuroprotection in the presence of ACA to alleviate neuroinflammation and ameliorate mitochondrial dysfunction.

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