Pharmacological Research 2000-09-01

Cerebroprotective drugs shorten the hypoxia-induced onset of electrical silence in unanesthetized rats.

Y Zagvazdin, M Bodo, A Sarkadi, L Szporny

Index: Pharmacol. Res. 42(3) , 261-8, (2000)

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Abstract

Pharmacological agents that delay the hypoxic arrest of neuronal electrical activity, as indicated by the suppression of electroencephalogram (EEG), have previously been thought to increase brain resistance to oxygen insufficiency. On the other hand, acceleration of the EEG suppression may offer some protection against severe hypoxia by reducing neuronal energy spending on electrogenesis. In unanesthetized rats we examined the effects of several antihypoxic drugs on the time of appearance of isoelectric EEG (tiEEG), caused by normobaric hypoxia. In addition, alterations in cerebral blood flow induced by hypoxia and by some drugs were monitored using polarographic techniques to determine if cerebrocirculatory changes play a significant role in the drug effects on tiEEG. We also assessed drug effects on behavioral recovery after hypoxia by measuring the latency of restoration of the head-withdrawal reflex upon vibrissae stimulation. Pentobarbital (30 and 60 mgkg(-1)i.p.), chloralhydrate (400 mgkg(-1)i.p.) flunarizine (50-100 mgkg(-1)p.o.), hydergine (3-50 mgkg(-1)p.o.), nicergoline (50 mgkg(-1)and 85 mgkg(-1)p.o.), sabeluzole (3 and 7.5 mgkg(-1)i.p.) and vincamine (80 mgkg(-1)p.o.) reduced tiEEG (mean 27.1 +/- 3.3 min prior to drugs). In contrast, idebenone (29-85 mgkg(-1)p.o.) and vinpocetine (29-85 mgkg(-1)p.o.) had no significant effects on tiEEG. The divergent effects on cerebral blood flow suggest an insignificant role for cerebrocirculatory changes in the drug-induced reduction of tiEEG during severe hypoxia. The drug effects on recovery of the head-withdrawal reflex (mean 4.2 +/- 1.3 min prior to drugs) varied from a delay (sabeluzole) to acceleration (flunarizine) with no correlation to the effects on tiEEG, suggesting that EEG criteria alone may not predict the course of functional recovery.Copyright 2000 Academic Press.