Perinatal asphyxia, hyperthermia and hyperferremia as factors inducing behavioural disturbances in adulthood: a rat model.

Abstract

Alertness was studied in adult male Wistar rats after neonatal critical anoxia applied under three different thermal conditions: (i) at physiological neonatal body temperature of 33 degrees C, (ii) at body temperature elevated to 37 degrees C, and (iii) at body temperature elevated to 39 degrees C (both during anoxia and for 2 h postanoxia). To elucidate the effect of iron-dependent postanoxic oxidative damage to the brain, half of the group (iii) was injected with deferoxamine, a chelator of iron. Postanoxic behavioural disturbances were recorded in open-field, elevated plus-maze, and sudden silence tests when the rats reached the age of 4 month. Moreover, spontaneous motor activity of the rats was recorded radiotelemetrically in their home-cages. Both open-field stress-induced and spontaneous motor activity were reduced in rats subjected to neonatal anoxia under hyperthermic conditions. In contrast, these rats were hyperactive in the plus-maze test. Both the plus-maze and sudden silence tests revealed that these rats show reduced alertness to external stimuli signalling potential dangers. The behavioural disturbances were prevented by the body temperature of 33 degrees C and by postanoxic administration of deferoxamine. These data support the conclusion that permanent postanoxic behavioural disturbances are due to iron-dependent oxidative damage to the brain, which can be prevented by the reduced neonatal body temperature.