title: Histological changes and neurotransmitter levels three months following perinatal asphyxia in the rat.
abstract: The involvement of excitatory amino acids (EAA) in the pathogenesis of hypoxic-ischemic states is well-documented. Information on the role of overexcitation by EAA in perinatalasphyxia (PA), however, is limited and data from adult models cannot be directly extrapolated to immature systems. Moreover, most adult models of ischemia are representing stroke rather than PA. We decided to study long term effects in a non-invasive rat model of PA resembling the clinical situation three months following the asphyctic insult. Morphometry on Nissl - stained sections was used to determine neuronal death in frontal cortex, striatum, hippocampus CA1, hypothalamus and cerebellum L1, and the amino acids glutamate, glutamine, aspartate, GABA, taurine, arginine as well as histamine, serotonin and 5-hydroxy-indoleacetic acid were determined in several brain regions and areas. Morphometry revealed that neuronal loss was present in the hippocampal area CA1 in all groups with PA and that morphological alterations were significantly higher in the cerebellar granular layer. The prominent light microscopical finding in all areas of asphyctic rats studied was decreased Nissl-staining, suggesting decreased cellular RNA levels. Glutamate, aspartate and glutamine were significantly elevated in the hypothalamus of asphyctic rats probably indicating overstimulation by EAA. Excitotoxicity in this area would be compatible with findings of emotional / behavioral deficits observed in a parallel study in our model of PA. Our observations point to and may help to explain behavioral and emotional deficits in Man with a history of perinatal asphyxia.
authors.affiliation: University of Vienna, Dpt of Pediatrics, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Kohlhauser
authors.forename: S
authors.initials: S
authors.lastname: Kaehler
authors.forename: W
authors.initials: W
authors.lastname: Mosgoeller
authors.forename: N
authors.initials: N
authors.lastname: Singewald
authors.forename: D
authors.initials: D
authors.lastname: Kouvelas
authors.forename: H
authors.initials: H
authors.lastname: Prast
authors.forename: H
authors.initials: H
authors.lastname: Hoeger
authors.forename: B
authors.initials: B
authors.lastname: Lubec
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism; D001237:Asphyxia / Q000503:physiopathology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006632:Histamine / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000166:cytology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013654:Taurine / Q000378:metabolism; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D005973:Glutamine; D013654:Taurine; D001224:Aspartic Acid; D012701:Serotonin; D018698:Glutamic Acid; D006897:Hydroxyindoleacetic Acid; D005680:gamma-Aminobutyric Acid; D006632:Histamine; D001120:Arginine