Expression of neural stem cell surface marker CD133 in balloon cells of human focal cortical dysplasia.
OBJECTIVE
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 (beta-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.
Ying
Zhong
Z
Department of Neurology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Gonzalez-Martinez
Jorge
J
Tilelli
Cristiane
C
Bingaman
William
W
Najm
Imad
I
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D019254:Genes, bcl-2 / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009421:Nervous System Malformations / Q000378:metabolism / Q000503:physiopathology; D064231:Nestin; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
D000071916:AC133 Antigen; D015703:Antigens, CD; D015415:Biomarkers; D006023:Glycoproteins; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; C000606023:PROM1 protein, human; D010455:Peptides