Abstracts

Rationale: There is mounting evidence of cortical developmental abnormalities from morphometric MRI studies in people with idiopathic generalized epilepsies (IGE). These findings were also reflected in the baboon model for IGE. In this preliminary study, we attempted to compare stereoscopically quantified heterotopic neurons in the molecular layer, cortical layer VI and subcortical white matter in baboons that were photosensitive to baboons with normal scalp EEG studies. Methods: Ten adult baboon (Papio hamadryas anubis and hybrids), ages 19 to 24 years old, were used in this study. Six baboons had generalized interictal epileptic discharges (IED+) on scalp EEG (three were photosensitive), while the four control (CTL) group had normal studies. None of the baboons had a history of seizures. Based upon prior MRI morphometric studies in baboons with IEDs on scalp EEG, three cortical sulci were selected for histopathological sampling: dorsal intraparietal (IPS), ventral lunate (LS), and anterior cingulate sulci (CGS). Postmortem samples of 1 cm3, which included both banks of adjacent gyri and the underlying white matter (WM), were collected within 30 minutes. Formalin-fixed paraffin embedded sections were stained with anti-NeuN primary antibody using indirect immunohistochemistry and diaminbenzidine as the chromogen. The sections were counterstained with hemotoxylin. Standard-sized rectangular areas of layers 1 and 6 and the subjacent WM were used to perform total cell counts of NeuN-positive neurons. Quantification was performed without knowledge of the baboons' EEg findings. Neuron densities of each sulcus and area were compared between control and epileptic animals with Student's t-test; p<0.05. Results: Density of NeuN neurons ranged from 22.2 to 668.7 per square millimeter with the lowest in the WM and highest in layer 6. There were no remarkable differences of density within layers across sulci. Only one sulcus (CGS) displayed a statistically significant (p<0.05) difference between control and epileptic groups. Conclusions: This preliminary study, shows that there are differences in neuronal counts between PS and CTL baboons, particularly in the frontal subcortical white matter. This finding is consistent with earlier histopathological studies in patients with juvenile myoclonic epilepsy. The increase of subcortical neurons may represent markers of abnormal cortical development in PS baboons. Additional baboons need to be studied to confirm these findings, including baboons with clinical seizures, with the ultimate goal of characterizing the heterotopic neurons, many of which may be subplate neurons.