title: Morphological evidence that xenon neuroprotects against N-methyl-DL-aspartic acid-induced damage in the rat arcuate nucleus: a time-dependent study.
abstract: The hyperactivation of glutamate receptors, especially those of the N-methyl-d-aspartate subtype (NMDA), can induce excess calcium entry into cells, leading to neuronal death. Since the anesthetic gas xenon behaves as an NMDA antagonist, the present article investigated, by distinct morphological approaches and after different times, the possible neuroprotectant effects of this gas in a model of neuronal damage induced by N-methyl-dl-aspartic acid (NMA) on rat arcuate nucleus. Rats were assigned to the following groups: controls; xenon exposure; NMA treatment; or xenon exposure + NMA treatment. Animals were placed in an experimental cage and after 10 min a mixture of xenon (or nitrogen) 70% and oxygen 30% was delivered. After 3 h, 1, 2, 5, or 7 days from gas exposure, rats were euthanized and the whole brain was removed and processed for either transmission electron microscopy or light microscopy. In the arcuate nucleus from NMA-treated animals only 40-60% of cell population survived in all times with several degenerating neurons giving the typical appearance of a "bull's eye." At ultrastructural level, chromatin margination, nuclear shrinkage, mitochondria with matrix dilution, dilated endoplasmic cisternae, and electrondense cytoplasm were detected. Xenon alone did not induce changes, but reduced of about 50% NMA-induced cell loss as well as degenerating neurons, with the maximal neuroprotection at 7 days. These results confirm that in the rat arcuate nucleus NMA can induce a severe neuronal damage that is already marked after 3 h. Xenon significantly reduced the neuronal damage at all times and can be then regarded as a promising neuroprotectant agent.
authors.affiliation: Department of Human Morphology and Applied Biology, University of Pisa, Via Roma 55, I-56126 Pisa, Italy. gianfranco.natale@anist.med.unipi.it
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Natale
authors.forename: Davide
authors.initials: D
authors.lastname: Cattano
authors.forename: Antonio
authors.initials: A
authors.lastname: Abramo
authors.forename: Francesco
authors.initials: F
authors.lastname: Forfori
authors.forename: Federica
authors.initials: F
authors.lastname: Fulceri
authors.forename: Francesco
authors.initials: F
authors.lastname: Fornai
authors.forename: Antonio
authors.initials: A
authors.lastname: Paparelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Giunta
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects* / Q000473:pathology; D004347:Drug Interactions; D005260:Female; D016202:N-Methylaspartate / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013996:Time and Motion Studies; D014978:Xenon / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D014978:Xenon; D016202:N-Methylaspartate