Seizures Induced by Homocysteine in Rats During Ontogenesis

Summary: We studied the convulsant action of homocysteine in 211 immature and adult Wistar albino rats. Homocysteine elicited minimal, predominantly clonic, and major generalized tonic-clonic seizures at six different developmental stages, from 7 days to adulthood. Nevertheless, some age-dependent differences in the seizure pattern were apparent. Minimal seizures in immature rats lasted ≤20 min, thus representing an epileptic status, whereas in adult animals these seizures were much shorter, lasting only ≥40 s. In addition, flexion seizures were observed in 7-and 12-day-old rats, only rarely in 15-and 18-day-old animals, and never in the 25-day-old and adult rats. ECoG recordings demonstrated a nearly iso-electric pattern during homocysteine-induced seizures in 7-and 12-day-old rat pups. In older rats, spikes or sharp waves were recorded, but precise electroclinical correlations were poor. The greater sensitivity of younger animals to kainic acid (KA) and N-methyl-D-aspartate (NMDA), as reported previously, was not evident in the case of homocysteine-induced seizures. This observation, together with a different behavioral pattern, suggests that homocysteine cannot be considered a simple agonist of the kainate or NMDA type of excitatory amino acid receptors. The exact mechanism of the convulsant action of homocysteine, both during development and in adulthood, remains to be clarified.