NEUROPEPTIDE-MEDIATED EXCITABILITY - A KEY TRIGGERING MECHANISM FOR SEIZURE GENERATION IN THE DEVELOPING BRAIN

Most human seizures occur early in life,consistent with established ex citability-promoting features of the developing brain. Surprisingly, t he majority of developmental seizures are not spontaneous but are prov oked by injurious or stressful stimuli, What mechanisms mediate 'trigg ering' of seizures and limit such reactive seizures to early postnatal life! Recent evidence implicates the excitatory neuropeptide, cortico tropin-releasing hormone (CRH), Stress activates expression of the CRH gene in several limbic regions, and CRH-expressing neurons are strate gically localized in the immature rat hippocampus, in which this neuro peptide increases the excitability of pyramidal cells in vitro. Indeed , in vivo, activation of CRH receptors - maximally expressed in hippoc ampus and amygdala during the developmental period which is characteri zed by peak susceptibility to 'provoked' convulsions - induces severe, age-dependent seizures, Thus, converging data indicate that activatio n of expression of CRH constitutes an important mechanism for generati ng developmentally regulated, triggered seizures, with considerable cl inical relevance.