NeuroanatomyExpression of layer-specific markers in the adult neocortex of BCNU-Treated rat, a model of cortical dysplasia
Section snippets
Animal treatment and tissue fixation
The experiments were performed in accordance with the guidelines defined by the European Communities Council Directive (86/609/EEC) and every effort was made to limit the number and suffering of animals used.
Pregnant Sprague–Dawley rats (Charles River Italia, Calco, Italy) were i.p. injected with 20 mg/kg of BCNU solution (5% sterile glucose in water at 4 mg/ml) at E (embryonic day) 15 (E1 was defined as the day of vaginal plug), at the time of peak cortical neurogenesis. On the same
Overview of the histological alterations found in BCNU-treated rats
Fig. 1 summarizes the most prominent histopathological features identified in BCNU-exposed brain. They included: (i) the disorganization of cortical layers I/II (Fig. 1A), (ii) the large nodular clusters of heterotopic neurons prevalently localized in the lowest part of the cortex and periventricular heterotopia (Fig. 1B) identified with CB immunolabeling, (iii) ectopic and inverted pyramidal neurons in cortical layers I/II (Fig. 1C) identified with SMI311 immunolabeling. Another striking
Discussion
We reported a comparative analysis of the expression of some layer-specific markers between control rats and a model of CD, namely BCNU-treated rats, with the aim of mapping the alterations in the distribution of the cortical laminae that characterize CD. Our findings concerning the details of cortical layering disruption revealed the neuronal composition of heterotopia, and our combined use of ISH and ICC demonstrated the origin of the heterotopic and dysmorphic neurons characterizing this
Conclusion
In conclusion, layer-specific markers turned out to be a useful means of examining the disorganized laminar architecture and ontology of neurons in a model of CD. Similarly they can be applied to the investigation of human neuropathology to reveal the details of cortical alterations and shed light on the interpretations of pathogenesis.
Acknowledgments
This work was supported by grants of the Italian Ministry of Health to C.F, Fondazione Banca del Monte di Lombardia, and EU grant “Functional Genomics and Neurobiology of Epilepsy” (EPICure) contract no. LSHM-CT-2006.0373315. We acknowledge the technical assistance of Ms. Sonoko Ohsawa.
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