title: Hypoxia-induced hyperexcitability in vivo and in vitro in the immature hippocampus.
abstract: Hypoxia is the most common cause of neonatal seizures and encephalopathy. We have previously developed an in vivo experimental model of perinatal hypoxia which exhibits age-dependent acute and chronic epileptogenic effects. Between postnatal day (P) 10-12, the rat exhibits acute seizure activity during global hypoxia, while no seizures are induced at earlier (P5) or older (P60) ages. Rats exposed to hypoxia between P10-12 have reduced seizure thresholds to chemical convulsants in adulthood. The nonNMDA antagonists NBQX appears to suppress both the acute and long term epileptogenic effects of hypoxia. The age-dependency of the hyperexcitable response to hypoxia in vivo can be reproduced in vitro using hippocampal slices. In Mg(2+)-free media, hypoxia induced ictal discharges within 60 s of onset in 79% of slices from normal P10 rat pups compared to 11% of adult slices (p < 0.001). Model systems such as that described here allow for correlation of in vitro and in vivo electrophysiology and should provide data regarding the pharmacological and physiological characteristics of hypoxia-induced seizure activity in the immature brain which could ultimately be applied to therapeutic strategies.
authors.affiliation: Department of Neurology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. jensen@al.tch.harvard.edu
authors.forename: F E
authors.initials: FE
authors.lastname: Jensen
authors.forename: C
authors.initials: C
authors.lastname: Wang
mesh_terms: D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects; D004594:Electrophysiology; D004833:Epilepsy, Temporal Lobe / Q000209:etiology / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development* / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D066298:In Vitro Techniques; D008140:Lorazepam / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats
chemical_list: D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D016291:Dizocilpine Maleate; D008140:Lorazepam