Protective effect of adaptation to hypoxia and its prolongation by pharmacological agents in rats prone to audiogenic epilepsy

Abstract

Cytophotometric determination of RNA in various brain structures of hypoxia-adapted and unadapted epilepsy-prone rats at different times after an epileptic seizure shows much smaller decreases in RNA levels and their much more rapid return to normal in the adapted than in the unadapted rats. The adaptation to hypoxia produces a marked anticonvulsive effect, and this effect is enhanced and prolonged considerably by pharmacotherapy.Key Words: adaptation to hypoxia; audiogenic epilepsy; therapy Adaptation to periodic hypobaric hypoxia has been shown to increase considerably the resistance of Krushinsky-Molodkina (KM) rats to audiogenic epilepsy [6][7][8][9], to which they are genetically predisposed. While it has been suggested that the activation of nucleic acid and protein syntheses and the elevation of RNA content ha the brain that occur during adaptation may play a role in the antiepileptic effect of the latter [12], the question of how an audiogenic convulsive seizure might affect RNA concentration ha neurons of various brain structures of hypoxia-adapted and unadapted animals has not been addressed. Nor is it known how long the anticonvulsive effect of adaptation is retained after a course of adaptation and whether this effect can be prolonged by pharmacological means.Accordingly, the objectives of this study were to measure RNA levels in neurons of various brain nuclei at different times after an audiogenic epiInstitute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow leptic seizure ha hypoxia-adapted and unadapted animals, to see how rapidly the resistance to audiogenic epilepsy declines after the termination of adaptation, and to f'md out whether and to what extent the resistance can be prolonged by pharmacological agents. MATERIALS AND METHODSThe study was conducted on male KM rats weighhag 160-180 g which all reacted to an audiogenic stimulus (an electric bell ring of 90 dB) by motor excitation that terminated in clonic convulsions. The rin~ng was stopped as soon as these were observed. Limiting the duration of acoustic stimulation prevents mortality and the development of extensive subdural hemorrhages in the rats [8,9], which makes the KM rat model a very convenient tool for evaluating the anticonvulsive effect of adaptation.Adaptation of the test rats to periodic hypoxia was achieved by elevating them to an "altitude" of

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