Altered spatial distribution of PV-cortical cells and dysmorphic neurons in the somatosensory cortex of BCNU-treated rat model of cortical dysplasia.
OBJECTIVE
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.
Moroni
Ramona Frida
RF
Unit of Clinical Epileptology and Experimental Neurophysiology, Fondazione IRCCS, Instituto Neurologico C. Besta, Milano, Italy.
Inverardi
Francesca
F
Regondi
Maria Cristina
MC
Panzica
Ferruccio
F
Spreafico
Roberto
R
Frassoni
Carolina
C
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000276:immunology; D064026:Calbindins; D002330:Carmustine / Q000494:pharmacology*; D054221:Classical Lissencephalies and Subcortical Band Heterotopias / Q000139:chemically induced / Q000473:pathology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D007395:Interneurons / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D054220:Malformations of Cortical Development / Q000139:chemically induced* / Q000473:pathology; D008431:Maternal-Fetal Exchange; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D010320:Parvalbumins / Q000276:immunology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000276:immunology; D013003:Somatosensory Cortex / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D000906:Antibodies; D064026:Calbindins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D005680:gamma-Aminobutyric Acid; D002330:Carmustine