DEVELOPMENTAL SPECTRUM OF THE EXCITOTOXIC CASCADE INDUCED BY IBOTENATE - A MODEL OF HYPOXIC INSULTS IN FETUSES AND NEONATES

Ibotenate, a glutamatergic agonist, was used to study the spectrum of excitoxic disturbances at different ages of cerebral development. Cult ures of whole mouse embryo were submitted to ibotenate at E8 for 20 h: during the phase of early premigratory differentiation; ibotenate did not induce any detectable histological lesion. During migration of su pragranular neurons, newborn hamsters intracerebrally injected at PO w ith ibotenate display neuronal migration disorders graded from nodular heterotopias to extensive laminar heterotopias mimicking some aspects of lissencephalic and double-cortex syndromes. After completion of ne uronal layer V, PO mice injected with ibotenate exhibit laminar neuron al depopulation of layer V-VIa mimicking human microgyria. At P5 in mo use, after completion of neuronal migration of the cortical layers and the formation of porencephalic cysts. This study emphasizes the drama tic role played by glutamate in brain development, in the occurrence o f neuronal migration disorders in the cortex, and in grey and white ma tter damage.