Palmitoylethanolamide attenuates neurodevelopmental delay and early hippocampal damage following perinatal asphyxia in rats

HERRERA MI, UDOVIN LD, KOBIEC T, TORO-URREGO N, KUSNIER CF, KÖLLIKER-FRERS RA, LUACES JP, OTERO-LOSADA M, CAPANI F

Frontiers in Behavioral Neuroscience

Frontiers

Año: 2022

1663-3563

Impaired gas exchange close to labor causes perinatal asphyxia (PA), aneurodevelopmental impairment factor. Palmitoylethanolamide (PEA) provedneuroprotective in experimental brain injury and neurodegeneration models.This study aimed to evaluate PEA effects on the immature-brain, i.e., earlyneuroprotection by PEA in an experimental PA paradigm. Newborn rats wereplaced in a 37◦C water bath for 19 min to induce PA. PEA 10 mg/kg, s.c.,was administered within the first hour of life. Neurobehavioral responses wereassessed from postnatal day 1 (P1) to postnatal day 21 (P21), recording the dayof appearance of several reflexes and neurological signs. Hippocampal CA1area ultrastructure was examined using electron microscopy. Microtubuleassociated protein 2 (MAP-2), phosphorylated high and medium molecularweight neurofilaments (pNF H/M), and glial fibrillary acidic protein (GFAP)were assessed using immunohistochemistry and Western blot at P21. Overthe first 3 weeks of life, PA rats showed late gait, negative geotaxis andeye-opening onset, and delayed appearance of air-righting, auditory startle,sensory eyelid, forelimb placing, and grasp reflexes. On P21, the hippocampalCA1 area showed signs of neuronal degeneration and MAP-2 deficit. PEAtreatment reduced PA-induced hippocampal damage and normalized thetime of appearance of gait, air-righting, placing, and grasp reflexes. Theoutcome of this study might prove useful in designing intervention strategiesto reduce early neurodevelopmental delay following PA.