Alterations in seizure mechanisms caused by oxygen high pressure, 1,1-dimethylhydrazine, and pyridoxine.
High pressure oxygen (HBO) and 1,1-dimethylhydrazine (UDMH) both cause grand mal seizures, brain glycogen degradation, and inhibition of glutamic acid decarboxylase (GAD). Brain glycogen degradation is a sudden process that is perhaps initiated by convulsions in the case of UDMH-poisoning, but a gradual decrease in glycogen is detectable before the onset of hyperbaric oxygen toxicity symptoms. UDMH injection causes consecutive convulsions that follow a predictable sequence. (Time to convulsions is referred to as the induction period, and time between convulsions as the interictal period.) After a single injection of UDMH, there is a gradual decrease in resistance to HBO during the induction period, measured as time to convulsions breathing 100% oxygen at 6 ATA; in the first interictal period, this time is only 4 1/2 min in comparison with a control value of 26 min for untreated rats. Administration of pyridoxine, a B6-vitamin, 2 h after UDMH injection in the first interictal period, resulted in an immediate tenfold increase in resistance to oxygen toxicity, from 4 1/2 to 48 min. Pyridoxine may reverse the inhibitary effect of UDMH on GAD, and there is perhaps an accumulation of substrate, which is made available when GAD inhibition is diminishing. Simultaneous injection of pyridoxine and UDMH causes no convulsions, no change in brain glycogen levels, and an unchanged or increased resistance to HBO, measured two and three hours after injection.
D000818:Animals; D001921:Brain / Q000378:metabolism; D003292:Convulsants; D004127:Dimethylhydrazines / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism; D006931:Hyperbaric Oxygenation; D008297:Male; D008763:Methylhydrazines / Q000494:pharmacology; D011736:Pyridoxine / Q000494:pharmacology; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000209:etiology*
D003292:Convulsants; D004127:Dimethylhydrazines; D008763:Methylhydrazines; D006003:Glycogen; D011736:Pyridoxine