Reduced density of parvalbumin- and calbindin D28k-immunoreactive neurons in experimental cortical dysplasia

Cortical dysplasia (CD) is a congenital brain malformation in humans that i s closely associated with intractable epilepsy. This study utilized an anim al model of CD, in utero irradiation in rats, to determine if experimental dysplastic cortex demonstrates a reduction in the density of inhibitory int erneurons. Fetal rats were exposed to external irradiation on gestational d ay 17 to produce diffuse CD and heterotopic grey matter. As adults, these r ats were processed for immunohistochemistry using primary antibodies for pa rvalbumin (PA), calbindin D28k (CA), the 67 kD subunit of glutamic acid dec arboxylase (GAD67), and cresyl violet staining. Quantitative methods were u sed to determine the density of immunoreactive neurons and cresyl violet-st ained neurons in the neocortex at the rostro-caudal level of the anterior c ommissure. Compared to control values, the density of PA- and CA-immunoreac tive neurons was reduced in dysplastic cortex. Density of glutamic acic dec arboxylase-immunoreactive neurons was not different between control and dys plastic cortex. Overall neuronal density, measured in cresyl violet-stained sections, was not significantly different between control and dysplastic c ortex. These data suggest a selective reduction in inhibitory interneurons in experimental CD cortex or an impaired ability for these neurons to produ ce PA and CA. (C) 1999 Elsevier Science B.V. Al rights reserved.