Cerebellar oxidative stress and fine motor impairment in adolescent rats exposed to hyperthermia-induced seizures is prevented by maternal caffeine intake during gestation and lactation

Abstract

Febrile seizures (FS) is one of the most common convulsive disorders in infants and young children that only occurs during the first years of life in humans, when the cerebellum is still developing. Several works have shown that maternal caffeine consumption during gestation and lactation can exert protective effects on developing brain under pathological conditions. Here, we have used an animal model of FS to know whether maternal caffeine consumption during gestation and lactation exhibited protective effects on rat cerebellum.Pregnant rats were allowed to freely drink water or caffeine (1 g/l) during gestation and lactation. At PD13, neonates were submitted to hyperthermia-induced seizures (HIS) whereas pups not subject to hyperthermic stimulus were used as controls. 48 h, 5 and 20 days after HIS, rats were killed and plasma membranes and cytosolic fractions were isolated from cerebella. The enzymatic activities of glutathione reductase, glutathione S-transferase, caspase-3, 5´-nucleotidase and the levels of thiobarbituric acid reacting substances, adenosine A1 and A2A receptors were studied in these preparations. Furthermore, rats were tested in balance beam test and footprint test 20 days after HIS (PD33) in order to investigate the effect on fine motor coordination and gait patterns.Results obtained suggest that maternal caffeine consumption during gestation and lactation exerts two kinds of beneficial effects on cerebellum from rats submitted to HIS: a) at short term, maternal caffeine abolishes hyperthermic seizures induced-oxidative stress and caspase-3 activation and b) in adolescent rats (PD33), maternal caffeine prevents fine motor coordination impairment and gait disturbances.