Altered spatial distribution of PV-cortical cells and dysmorphic neurons in the somatosensory cortex of BCNU-treated rat model of cortical dysplasia

Abstract

Purpose: Cortical dysplasia (CD) represents a wide range of histopathological abnormalities of the cortical mantle that are frequently associated with drug-resistant epilepsy. Recently, carmustine (1-3-bis-chloroethyl-nitrosurea [BCNU]), given to pregnant rats on embryonic day (E) 15, has been used to develop an experimental model mimicking human CD. The aim of this study was to characterize cytological and histological alterations in this model, and compare the results with those observed in human CD.

Methods: Pregnant rats were given intraperitoneal injections of BCNU on E15. Sections of cerebral cortex from adult BCNU-treated rats were cytoarchitecturally and immunohistochemically analyzed using anti-SMI311, anticalbindin (CB), and antiparvalbumin (PV) antibodies. The density of the PV-immunoreactive (PV-ir) interneurons was quantitatively assessed by means of a two-dimensional cell-counting technique, and the spatial distribution of PV-ir neurons was evaluated by using the Voronoi tessellation.

Results: The morphological features included reduced cortical size, laminar disorganization, and heterotopic clusters of neurons. We also identified large, disoriented SMI311-positive pyramidal neurons, and dysmorphic neurons intensely immunostained for neurofilaments, similar to those observed in human dysplastic cortex. An altered distribution of PV-immunoreactive cortical interneurons was also present.

Conclusions: Although some of the cytoarchitectural abnormalities found in BCNU-exposed cortex are similar to those found in other CD models, we identified new alterations that recall the neuropathological description of type IIA (Taylor's type) CD. BCNU-treated rat could therefore be a useful additional model for investigating the pathogenic mechanisms involved in this CD.