Seizure Disorders Sex Hormones and Prognosis of Neonatal Seizures

The influence of testosterone on the development of the substantia nigra pars reticulata (SNR), a brain region involved in the control of seizures, was investigated in male rats castrated at birth, in experiments at Albert Einstein College ofMedicine and Montefiore Medical Center, Bronx, NY. Neonatal castration alters the maturation of the muscimol (GABA-A)-sensitive SNR effect on seizures. Microinfusions of muscimol in the SNR in neonatal rats castrated at 15 days postnatally (PN15) had no effect on seizures, irrespective of the infusion site within the SNR. In PN25 and 30 neonatally castrated rats, muscimol infusions had an anticonvulsant effect when injected into the SNRanterior but not posterior locations. The expression of a proconvulsant region in the SNR occurs only in the presence of testosterone in the immediate postnatal period. The development of the proconvulsant region at PN15 is triggered by restoring testosterone levels in neonatally castrated rats or by artificially increasing testosterone levels in females. The demonstration of sex-related differences in the SNR points to postnatal testosterone as a critical factor in the development of proor anticonvulsant circuits in the developing brain. (Veliskova J, Claudio 01, Galanopoulou AS et al. Seizures in the developing brain. Epilepsia December 2004;45 (Suppl 8):6-12). (Reprints: Dr J Veliskova, Department ofNeurology, K312, Albert Einstein College ofMedicine, 1410 Pelham Parkway South, Bronx, NY 10461).