OLEOYLETHANOLAMIDE AND PALMITOYLETHANOLAMIDE PROTECT CULTURED CORTICAL NEURONS AGAINST HYPOXIA

PORTAVELLA, MANUEL; RODRÍGUEZ-ESPINOSA, NIEVES ; GALEANO, PABLO; BLANCO, EDUARDO; ROMERO, JUAN IGNACIO; HOLUBIEC, MARIANA INÉS; RODRÍGUEZ DE FONSECA, FERNANDO; FERNÁNDEZ ESPEJO, EMILIO

CANNABIS AND CANNABINOID RESEARCH

Mary Ann Liebert, Inc.

Año: 2018 vol. 3 p. 171 - 178

Introduction Perinatal hypoxia-ischemia encefalopathy is defined as a neurological syndrome where the newborn suffers from acute ischemia and hypoxia during the perinatal period. New therapies are needed. The acylethanolamides oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) possess neuroprotective properties, and they could be effective against perinatal hypoxia ischemia. These lipid mediators act through peroxisome proliferator activated receptors subtype alpha (PPARalpha) or transient vanilloid receptors (TRPV) such as TRPV subtype 1 and 4. Material and methods The objectives of this study were to discern a) the neuroprotective role of OEA and PEA in parieto temporal cortical neurons of newborns rats and mice subjected to hypoxia and b) the role of the receptors PPARalpha, TRPV1 and TRPV4 in neuroprotective effects. Cell culture of cortical neurons and the lactate dehydrogenase assay were carried out. The role of receptors was discerned by using selective antagonist and agonist ligands as well as knock out PPARalpha mice. Results The findings indicate that OEA and PEA exert neuroprotective effects on cultured cortical neurons subjected to a hypoxic episode. These protective effects are not mediated by the receptors PPARα or TRPV1 or TRPV4, because neither PPARalpha knock out mice nor receptor ligands significantly modify OEA and PEA induced effects. Blocking TRPV4 with RN1734 is neuroprotective per se, and cotreatment with OEA and PEA is able to enhance neuroprotective effects of the acylethanolamides. Since stimulating TRPV4 was devoid of effects on OEA and PEA induced protective effects, effects of RN1734 cotreatment seem to be a consequence of additive actions. Conclusion The lipid mediators OEA and PEA exert neuroprotective effects on cultured cortical neurons subjected to hypoxia. Coadministration of OEA or PEA and the TRPV4 antagonist RN1734 is able to enhance neuroprotective effects. These in vitro results could be of utility for developing new therapeutic tools against perinatal hypoxia ischemia