Abstract

The present proposal is to investigate central nervous system (CNS) plasticity following metabolic insults occurring at birth, exploring the issue of conditioned vulnerability. The issue is studied with organotypic cultures prepared from asphyxia-exposed and caesarean-delivered-control rats, focusing on cell survival and neuronal development of basal ganglia; mesolimbic, and hippocampal pathways. Sentinel proteins and molecules involved in energy metabolism and immune responses are also evaluated, as well as markers of epigenetics. Vulnerability to subsequent metabolic insults is evaluated by exposing selected organotypic cultures from asphyxia-exposed and caesarean-delivered control pups to sub toxic concentrations of peroxide (H2O2), added to a glucose free culture medium for 24h. The hypothesis is that perinatal asphyxia primes CNS development, increasing the vulnerability to subsequent metabolic insults. The aim is to identify relevant markers for that vulnerability, providing targets for therapeutic strategies. Based in previous results, nicotinamide is used as a lead for putative neuroprotective compounds.