Experimentally induced leptomeningeal glioneuronal heterotopia and underlying cortical dysplasia of the lateral limbic area in rats treated transplacentally with methylmercury.

Leptomeningeal glioneuronal heterotopia (LGH) is a developmental anomaly sometimes observed at the surface of human brains with severe malformations. We experimentally induced LGH in brains of rat pups by transplacental exposure to methylmercury. Histopathological profiles of the induced LGH, including the spatio-temporal predominance of the manifestation, suggest some aspects of the histogenesis of this malformation. Pregnant rats on embryonic day 8 (E8), E11, E13, E16, E18 or E21 were treated orally with a single administration of 20 mg/kg methylmercury chloride, and the brains of their delivered offspring were examined on postnatal day 7 (P7) and P28. The incidence of LOH varied significantly according to the treatment day: it was almost exclusively restricted to individuals treated on E13. Furthermore, all the induced LGH was confined to the subarachnoid space dorsal to the rhinal fissure, unilaterally or bilaterally. A part of the nest was connected to the underlying cortical surface of the lateral limbic area, where glia limitans and basal lamina were disrupted. Narrow stripes of disarrangement of cortical neurons underlying the bridges were observed. The P7 LGHs consisted mainly of neurons, some of which were GABA-immunolabeled. and a small number of astrocytes as well as endogenous blood vessels and fibroblasts. LGHs in P28 brains consisted mainly of GFAP-positive astrocyte processes. An additional experiment with double administrations of 5-bromo-2-deoxyuridine (BrdU) and methylmercury on E13 disclosed an abnormally widespread distribution of labeled neurons throughout all cortical layers underlying the LGH in P28 brains. Thus, cerebral LGH would be induced if a developing brain were insulted at the early stage of neurogenesis. accompanied by cortical dysplasia.