Summary:Cortical dysplasia (CD, also known as malformations of cortical development) are the pathological substrates in a large percentage of patients with pharmacoresistant epilepsy who may be amenable to surgical treatment. Therefore, research on the mechanisms of dysplastic lesion formation and epileptogenicity is of paramount importance for the prevention, detection, and treatment of CD-induced epilepsy. The purpose of this review is to discuss and critically evaluate the current state and results of human tissue experimentation (focusing on reported results of studies done on neocortical dysplastic tissue resected from patients with pharmacoresistant epilepsy), and to discuss some of the concerns related to research that uses surgically resected epileptic human tissue. The use of better animal models of CD as a tool toward the better understanding of the mechanisms of pathogenesis, epileptogenesis, and epileptogenicity of dysplastic lesions will be reviewed from the perspective of their usefulness in a model of translational research that should ultimately result in better diagnostic and therapeutic techniques of CD.

Summary:  Purpose: Focal cortical dysplasia (CD) is characterized by the presence of dysmorphic neurons, laminar and columnar disorganization. A few patients with CD have balloon cells intermixed with dysmorphic neurons. The cellular characteristics of balloon cells remain unknown. This study was intended to determine further the cellular characteristics of balloon cells. Methods: Neocortical tissue resected from five patients with medically intractable focal epilepsy due to CD was studied. The presence of balloon cells (large opalescent cells with eccentric nuclei) was confirmed in all five patients by using cresylecht violet staining. Immunocytochemistry used antibodies against markers of pluripotential stem cells (CD133), multipotential progenitor cells (nestin), antiapoptotic gene products (Bcl‐2), immature neurons (β‐tubulin 3, TUJ1), immature glia (vimentin), mature neurons (MAP2 and NeuN), and astrocytes (glial fibrillary acidic protein; GFAP). Results: Balloon cells (BCs) were found to be immunoreactive to Bcl‐2 (46%), vimentin (41%), Nestin (28%), CD133 (28%), MAP2 (27%), GFAP (14%), and TUJ1 (10%). An extremely small number of BCs were immunopositive for NeuN. Confocal double labeling showed that balloon cells were dually immunopositive for CD133/nestin; CD133/GFAP; CD133/Bcl‐2, and nestin/GFAP. Conclusions: These results show that balloon cells are heterogeneous cell populations expressing cell‐surface markers for pluripotential stem cells and proteins for multipotent progenitors, or immature neurons/glia. The presence of stem cell/progenitor markers in the balloon cells could be due to a persistent postnatal neurogenesis or early embryonic insult that resulted in arrest of proliferation/differentiation at their early stages. Additionally, the coexpression of Bcl‐2 in CD133‐positive balloon cells suggests that a resistance to programmed cell death may be involved in the pathogenesis of cortical dysplasia.

The aims of this study were to characterize the spatial distribution of neurodegeneration after status epilepticus (SE) induced by either systemic (S) or intrahippocampal (H) injection of pilocarpine (PILO), two models of temporal lobe epilepsy (TLE), using FluoroJade (FJ) histochemistry, and to evaluate the kinetics of FJ staining in the H-PILO model. Therefore, we measured the severity of behavioral seizures during both types of SE and also evaluated the FJ staining pattern at 12, 24, and 168 h (7days) after the H-PILO insult. We found that the amount of FJ-positive (FJ+) area was greater in SE induced by S-PILO as compared to SE induced by H-PILO. After SE induced by H-PILO, we found more FJ+ cells in the hilus of the dentate gyrus (DG) at 12 h, in CA3 at 24 h, and in CA1 at 168 h. We found also no correlation between seizure severity and the number of FJ+ cells in the hippocampus. Co-localization studies of FJ+ cells with either neuronal-specific nuclear protein (NeuN) or glial fibrillary acidic protein (GFAP) labeling 24 h after H-PILO demonstrated spatially selective neurodegeneration. Double labeling with FJ and parvalbumin (PV) showed both FJ+/PV+ and FJ+/PV- cells in hippocampus and entorhinal cortex, among other areas. The current data indicate that FJ+ areas are differentially distributed in the two TLE models and that these areas are greater in the S-PILO than in the H-PILO model. There is also a selective kinetics of FJ+ cells in the hippocampus after SE induced by H-PILO, with no association with the severity of seizures, probably as a consequence of the extra-hippocampal damage. These data point to SE induced by H-PILO as a low-mortality model of TLE, with regional spatial and temporal patterns of FJ staining.

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The ApoE-epsilon4 allele interacts with longstanding seizures to affect memory performance, both verbal and nonverbal, in patients with medically intractable temporal lobe epilepsy.