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Behav. Neurosci."],"abstract":"<jats:p>Impaired gas exchange close to labor causes perinatal asphyxia (PA), a neurodevelopmental impairment factor. Palmitoylethanolamide (PEA) proved neuroprotective in experimental brain injury and neurodegeneration models. This study aimed to evaluate PEA effects on the immature-brain, i.e., early neuroprotection by PEA in an experimental PA paradigm. Newborn rats were placed in a 37\u00b0C water bath for 19 min to induce PA. PEA 10 mg\/kg, s.c., was administered within the first hour of life. Neurobehavioral responses were assessed from postnatal day 1 (P1) to postnatal day 21 (P21), recording the day of appearance of several reflexes and neurological signs. Hippocampal CA1 area ultrastructure was examined using electron microscopy. Microtubule-associated protein 2 (MAP-2), phosphorylated high and medium molecular weight neurofilaments (pNF H\/M), and glial fibrillary acidic protein (GFAP) were assessed using immunohistochemistry and Western blot at P21. Over the first 3 weeks of life, PA rats showed late gait, negative geotaxis and eye-opening onset, and delayed appearance of air-righting, auditory startle, sensory eyelid, forelimb placing, and grasp reflexes. On P21, the hippocampal CA1 area showed signs of neuronal degeneration and MAP-2 deficit. PEA treatment reduced PA-induced hippocampal damage and normalized the time of appearance of gait, air-righting, placing, and grasp reflexes. The outcome of this study might prove useful in designing intervention strategies to reduce early neurodevelopmental delay following PA.<\/jats:p>","DOI":"10.3389\/fnbeh.2022.953157","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T05:57:14Z","timestamp":1661407034000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Palmitoylethanolamide attenuates neurodevelopmental delay and early hippocampal damage following perinatal asphyxia in rats"],"prefix":"10.3389","volume":"16","author":[{"given":"Maria I.","family":"Herrera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas D.","family":"Udovin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Kobiec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Toro-Urrego","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos F.","family":"Kusnier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolfo A.","family":"K\u00f6lliker-Frers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan P.","family":"Luaces","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Otero-Losada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Capani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,25]]},"reference":[{"key":"B1","first-page":"518","article-title":"Perinatal asphyxia","author":"Adcock","year":"2008","journal-title":"Manual of neonatal care"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1016\/j.bbi.2012.07.021","article-title":"Administration of palmitoylethanolamide (PEA) protects the neurovascular unit and reduces secondary injury after traumatic brain injury in mice.","volume":"26","author":"Ahmad","year":"2012","journal-title":"Brain Behav. 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