Palmitic acid methyl ester is a novel neuroprotective agent against cardiac arrest

Reggie Hui-Chao Lee; Alexandre Couto E Silva; HarLee E Possoit; Francesca M Lerner; Po-Yi Chen; Rinata Azizbayeva; Cristiane T Citadin; Celeste Yin-Chieh Wu; Jake T Neumann; Hung Wen Lin

doi:10.1016/j.plefa.2018.11.011

Palmitic acid methyl ester is a novel neuroprotective agent against cardiac arrest

Prostaglandins Leukot Essent Fatty Acids. 2019 Aug:147:6-14. doi: 10.1016/j.plefa.2018.11.011. Epub 2018 Nov 23.

Affiliations

¹ Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, USA; Center for Brain Health, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
² Center for Brain Health, Louisiana State University Health Sciences Center, Shreveport, LA, USA; Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
³ Department of Neurology, Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, Miami, FL, USA.
⁴ Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, USA; Center for Brain Health, Louisiana State University Health Sciences Center, Shreveport, LA, USA; Department of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan.
⁵ Department of Biomedical Sciences, West Virginia School of Osteopathic Medicine, Lewisburg, WV, USA.
⁶ Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, USA; Center for Brain Health, Louisiana State University Health Sciences Center, Shreveport, LA, USA; Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, LA, USA. Electronic address: hlin2@lsuhsc.edu.

Abstract

We previously discovered that palmitic acid methyl ester (PAME) is a potent vasodilator first identified and released from the superior cervical ganglion and remain understudied. Thus, we investigated PAME's role in modulating cerebral blood flow (CBF) and neuroprotection after 6 min of cardiac arrest (model of global cerebral ischemia). Our results suggest that PAME can enhance CBF under normal physiological conditions, while administration of PAME (0.02 mg/kg) immediately after cardiopulmonary resuscitation can also enhance CBF in vivo. Additionally, functional learning and spatial memory assessments (via T-maze) 3 days after asphyxial cardiac arrest (ACA) suggest that PAME-treated rats have improved learning and memory recovery versus ACA alone. Furthermore, improved neuronal survival in the CA1 region of the hippocampus were observed in PAME-treated, ACA-induced rats. Altogether, our findings suggest that PAME can enhance CBF, alleviate neuronal cell death, and promote functional outcomes in the presence of ACA.

Keywords: Cardiac arrest; Cerebral blood flow; Global ischemia; Hypoperfusion; Neuroprotection; Palmitic acid methyl ester.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
CA1 Region, Hippocampal / drug effects*
Cardiopulmonary Resuscitation
Cerebrovascular Circulation / drug effects
Disease Models, Animal
Heart Arrest / prevention & control*
Heart Arrest / therapy
Learning / drug effects
Neuroprotective Agents / administration & dosage*
Neuroprotective Agents / pharmacology
Palmitates / administration & dosage*
Palmitates / pharmacology
Rats
Rats, Sprague-Dawley
Spatial Memory / drug effects

Substances

Neuroprotective Agents
Palmitates
methyl palmitate

Grants and funding

R01 NS096225/NS/NINDS NIH HHS/United States