The epileptogenic effect of seizures induced by hypoxia: the role of NMDA and AMPA/KA antagonists.
Hypoxia of the brain may alter further seizure susceptibility in a different way. In this study, we tried to answer the question how episode of convulsion induced by hypoxia (HS) changes further seizure susceptibility, and how N-methyl-D-aspartic acid (NMDA) and AMPA/KA receptor antagonists influence this process. Adult Albino Swiss mice exposed to hypoxia (5% O(2)) developed clonic/tonic convulsions after about 340 s. Mice which underwent 10 s but not 5 s seizures episode subsequently exhibited significantly increased seizure susceptibility to low doses (equal ED(16)) of bicuculline (BCC) and NMDA during a 3-week observation period. No morphological signs of brain tissue damage were seen in light microscope on the third day after a hypoxia-induced seizure (HS). Learning abilities assessed in passive avoidance test as well as spontaneous alternation were not disturbed after an HS episode. Pretreatment with AMPA/KA receptor antagonist NBQX effectively prolonged latency to HS and given immediately after seizure episode also attenuated subsequent convulsive susceptibility rise, however, NMDA receptor antagonist, MK-801, appeared to be ineffective. These results suggest that a seizure episode induced by hypoxia, depending on its duration, may play an epileptogenic role. The AMPA/KA receptor antagonist prolongs the latency to HS, and given after this episode, prevents the long-term epileptogenic effect.
Rubaj
Andrzej
A
Department of Cardiology, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland. arubaj@yahoo.com
Zgodziński
Witold
W
Sieklucka-Dziuba
Maria
M
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001640:Bicuculline / Q000633:toxicity; D001923:Brain Chemistry / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004827:Epilepsy / Q000503:physiopathology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D018756:GABA Antagonists / Q000633:toxicity; D000860:Hypoxia / Q000503:physiopathology*; D051379:Mice; D016202:N-Methylaspartate / Q000633:toxicity; D011810:Quinoxalines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D001640:Bicuculline