Correlative Structural, Biochemical and Behavioral Study in Neuroprotection with Palmitoylehanolamide after Perinatal Asphyxia in the Immature Brain

Abstract

Perinatal asphyxia (PA) is an obstetric complication associated with an impaired gas exchange.Diminish in the oxygen levels prompted short and long-term alterations in synapses and relatedstructures that are related to neuronal dysfunction and death. This serious health problem could lead toneonatal mortality and continues to be a determinant of several neurodevelopmental disorders. The lackof knowledge about the proper neuroprotective agents prompted us to investigate the role ofPalmitoylethanolamide (PEA) in the experimental treatment of PA. This natural occurring amide hasexerted protective effects in several models of brain injury and neurodegeneration.For this study, we used a well-established murine model of PA [1]. After one, of moderate PA (19 min)one group of rats were sacrificed and their brains were analyzed by combining immunohistochemistry,conventional electron microscopy, and 3-D reconstruction. The other group was subjected tobehavioural analysis [2].After one month of the PA insult, we observed an augmentation in CA1 neuronal nucleus degenerationusing electron microscopy (Fig 1). Immunohistochemistry revealed a significant increase for pNF H/Mand decrease in MAP-2 in CA1 reactive area. These changes were also observed when analyzing thelevel of expression of these markers by western blot. Vertical exploration impairments and anxietyrelated behaviors were encountered in the OF and EPM tests. PEA treatment attenuated PA-inducedhippocampal damage and its corresponding behavioral alterations.These results contribute to the elucidation of PEA neuroprotective role after PA and the futureestablishment of therapeutic strategies for the developing brain.