title: Neonatal hypoxic-ischemic encephalopathy reduces c-Fos activation in the rat hippocampus: evidence of a long-lasting effect.
abstract: The effect of neonatal hypoxic-ischemic encephalopathy (HIE) on maturation of nociceptive pathways has been sparsely explored. To investigate whether neonatal HIE alters neuronal activity, nociceptive behavior, and serum neuroplasticity mediators (brain-derived neurotrophic factor [BDNF] and tumor necrosis factor-α [TNF]) in the short, medium, and long term. Neonate male Wistar rats were randomized to receive a brain insult that could be either ischemic (left carotid artery ligation [LCAL]), hypoxic (8% oxygen chamber), hypoxic-ischemic (LCAL and hypoxic chamber), sham-ischemic, or sham-hypoxic. Neuronal activity (c-Fos activation at region CA1 and dentate gyrus of the hippocampus), nociceptive behavior (von Frey, tail-flick, and hot-plate tests), neuroplasticity mediators (BDNF, TNF), and a cellular injury marker (lactase dehydrogenase [LDH]) were assessed in blood serum 14, 30, and 60 days after birth. Neonatal HIE persistently reduced c-Fos activation in the ipsilateral hippocampal region CA1; however, contralateral c-Fos reduction appeared only 7 weeks after the event. Neonatal HIE acutely reduced the paw withdrawal threshold (von Frey test), but this returned to normal by the 30th postnatal day. Hypoxia reduced serum LDH levels. Serum neuroplasticity mediators increased with age, and neonatal HIE did not affect their ontogeny. Neonatal HIE-induced reduction in neuronal activity occurs acutely in the ipsilateral hippocampal region CA1 and persists for at least 60 days, but the contralateral effect of the insult is delayed. Alterations in the nociceptive response are acute and self-limited. Serum neuroplasticity mediators increase with age, and remain unaffected by HIE.
authors.affiliation: Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul, 90035-003, Porto Alegre, Brazil; Pain Pharmacology and Animal Models of Neuromodulation Laboratory, Department of Pharmacology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, 90050-170, Porto Alegre, Brazil; Animal Experimentation Unit, Hospital de Clínicas de Porto Alegre Graduate Research Group, 90035-003, Porto Alegre, Brazil; Graduate Program in Health and Human Development, Centro Universitário Unilasalle, 92010-000, Canoas, Brazil.
authors.forename: Andressa
authors.initials: A
authors.lastname: Souza
authors.affiliation: Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul, 90035-003, Porto Alegre, Brazil.
authors.forename: Jairo Alberto
authors.initials: JA
authors.lastname: Dussan-Sarria
authors.affiliation: Graduate Program in Biological Sciences: Physiology, Universidade Federal do Rio Grande do Sul, 90035-003, Porto Alegre, Brazil; Pain Pharmacology and Animal Models of Neuromodulation Laboratory, Department of Pharmacology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, 90050-170, Porto Alegre, Brazil; Animal Experimentation Unit, Hospital de Clínicas de Porto Alegre Graduate Research Group, 90035-003, Porto Alegre, Brazil.
authors.forename: Liciane Fernandes
authors.initials: LF
authors.lastname: Medeiros
authors.affiliation: Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul, 90035-003, Porto Alegre, Brazil; Pain Pharmacology and Animal Models of Neuromodulation Laboratory, Department of Pharmacology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, 90050-170, Porto Alegre, Brazil; Animal Experimentation Unit, Hospital de Clínicas de Porto Alegre Graduate Research Group, 90035-003, Porto Alegre, Brazil.
authors.forename: Ana Cláudia
authors.initials: AC
authors.lastname: Souza
authors.affiliation: Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul, 90035-003, Porto Alegre, Brazil; Pain Pharmacology and Animal Models of Neuromodulation Laboratory, Department of Pharmacology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, 90050-170, Porto Alegre, Brazil; Animal Experimentation Unit, Hospital de Clínicas de Porto Alegre Graduate Research Group, 90035-003, Porto Alegre, Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: Oliveira
authors.affiliation: Graduate Program in Biological Sciences: Physiology, Universidade Federal do Rio Grande do Sul, 90035-003, Porto Alegre, Brazil; Pain Pharmacology and Animal Models of Neuromodulation Laboratory, Department of Pharmacology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, 90050-170, Porto Alegre, Brazil; Animal Experimentation Unit, Hospital de Clínicas de Porto Alegre Graduate Research Group, 90035-003, Porto Alegre, Brazil.
authors.forename: Vanessa Leal
authors.initials: VL
authors.lastname: Scarabelot
authors.affiliation: Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul, 90035-003, Porto Alegre, Brazil; Pain Pharmacology and Animal Models of Neuromodulation Laboratory, Department of Pharmacology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, 90050-170, Porto Alegre, Brazil; Animal Experimentation Unit, Hospital de Clínicas de Porto Alegre Graduate Research Group, 90035-003, Porto Alegre, Brazil.
authors.forename: Lauren Naomi
authors.initials: LN
authors.lastname: Adachi
authors.affiliation: Department of Morphological Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Brazil.
authors.forename: Elisa Cristiana
authors.initials: EC
authors.lastname: Winkelmann-Duarte
authors.affiliation: Department of Morphological Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Brazil.
authors.forename: Bárbara Beatriz
authors.initials: BB
authors.lastname: Philippi-Martins
authors.affiliation: Pain Pharmacology and Animal Models of Neuromodulation Laboratory, Department of Pharmacology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, 90050-170, Porto Alegre, Brazil.
authors.forename: Carlos Alexandre
authors.initials: CA
authors.lastname: Netto
authors.affiliation: Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul, 90035-003, Porto Alegre, Brazil.
authors.forename: Wolnei
authors.initials: W
authors.lastname: Caumo
authors.affiliation: Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul, 90035-003, Porto Alegre, Brazil; Graduate Program in Biological Sciences: Physiology, Universidade Federal do Rio Grande do Sul, 90035-003, Porto Alegre, Brazil; Pain Pharmacology and Animal Models of Neuromodulation Laboratory, Department of Pharmacology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, 90050-170, Porto Alegre, Brazil; Animal Experimentation Unit, Hospital de Clínicas de Porto Alegre Graduate Research Group, 90035-003, Porto Alegre, Brazil. Electronic address: iracitorres@gmail.com.
authors.forename: Iraci L S
authors.initials: IL
authors.lastname: Torres
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000097:blood / Q000150:complications / Q000473:pathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D010147:Pain Measurement; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016760:Proto-Oncogene Proteins c-fos; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase
keywords: BDNF; Neonatal hypoxia–ischemia encephalopathy; Nociceptive behavior; TNF-α; c-Fos protein