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. Cultures 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 supragranular neurons, newborn hamsters intracerebrally injected at PO with 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 neuronal layer V, PO mice injected with ibotenate exhibit laminar neuronal depopulation of layer V-VIa mimicking human microgyria. At P5 in mouse, after completion of neuronal migration of the cortical plate, ibotenate induces neuronal loss in all cortical layers and the formation of porencephalic cysts. This study emphasizes the dramatic role played by glutamate in brain development, in the occurrence of neuronal migration disorders in the cortex, and in grey and white matter damage.