MECHANISMS IN THE INDUCTION OF NEURONAL HETEROTOPIAE FOLLOWING PRENATAL CYTOTOXIC BRAIN-DAMAGE

Prenatal exposure to several neuroteratogens, such as ionizing radiati on, ethanol, and cytotoxic drugs, induces the development of clusters of abnormally positioned neurons within the brain. These abnormalities have always been presumed to result from interference with normal neu ronal migration, presumably via effects on radial glia. In our study, pregnant rats were injected with methylazoxymethanol acetate (MAM) on either E13, E14, or E15. Computerised reconstruction techniques, Golgi and immunocytochemical staining as well as electron microscopy were u sed to detect structural abnormalities of radial glia which might be r esponsible for the production of heterotopiae. Several structural abno rmalities such as microcavitation, involvement of radial glial element s in rosettes, disturbance of the normal ventricular lining, and disru ption of the attachment of radial glial endfeet to the pial surface we re identified. We propose that periventricular heterotopiae result fro m disruption of the palisade arrangement of neuroepithelial cells in t he ventricular zone and the involvement of radial glial elements in ro settes. Layer I heterotopiae may arise from abnormalities of the dista l segments of radial glia and their attachment to the pia. No prenatal abnormalities in radial glia of the hippocampus were noted following MAM exposure at any of the 3 ages, consistent with the proposition tha t hippocampal heterotopiae arise by postnatal movements of pyramidal n eurons without radial glial involvement.