Immunohistochemical expression of fibroblast growth factor (FGF)-2 in epilepsy-associated malformations of cortical development (MCDs)

Department of Child Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan.
Neuropathology (Impact Factor: 1.65). 08/2008; 28(4):372-81. DOI: 10.1111/j.1440-1789.2007.00881.x
Source: PubMed


To elucidate the biological significance of dysplastic cells in malformations of cortical development, an immunohistochemical study was performed to investigate fibroblast growth factor-2 (FGF-2) expression in corticectomy specimens from epilepsy patients, including focal cortical dysplasia (FCD) with balloon cells (BCs) (n=4; age/sex=2M, 14F, 24M, 45M), tubers of tuberous sclerosis complex (TSC-tubers) (n=2; 1F, 3F), FCD without BCs (n=3; 23F, 23M, 25M), and gliotic lesions (n=3; 12M, 25M, 29M). The nucleus and/or cytoplasm of astrocytes in all cases examined were positive for FGF-2; however, FGF-2 immunoreactivity was not detected in oligodendroglial cells. In all dysplastic lesions, FGF-2 was detected in the astrocytic nuclei, and cytoplasm and/or nuclei of BCs. Dysplastic neurons (DNs) in FCD with BCs and TSC-tubers were variably positive for FGF-2 in the cytoplasm, but FGF-2 was not detected in the neurons of FCD without BCs. The number of FGF-2 immunoreactive cells (FGF-2-IR%) in FCD with BCs (46.0+/-4.1%) was higher than that in FCD without BCs (19.8+/-3.1%) and gliotic lesions (19.5+/-3.3%) with statistical significance (P<0.001). These results, together with previous reports showing FGF-2 expression in neuroblasts and glioblasts in human fetal brain, and mainly in astrocytes in adult brain, suggest that FGF-2 expression in MCDs reflects incomplete differentiation and maturation of dysplastic cells, and that FGF-2-IR% is associated with histological subtypes of MCD, reflecting the timing of insults underlying the pathogenesis of each disorder.

Download full-text


Available from: Hajime Miyata
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Synthesizing hazard-free asynchronous circuits directly at signal transition graph (STG) level has been shown to need significantly less CPU time than approaches at the state-graph. However, all previous methods at STG level were based on sufficient conditions only. Hence, the synthesized circuit results generally are inferior, due to the incomplete transformation. We present a new characteristic graph (CG) to encapsulate all feasible solutions of the original STG in reduced size, which compares favorably with the state graph approach. The requirements of speed independent circuits can then be completely transformed into the CG. Furthermore, we derive a necessary and sufficient condition for speed independent implementation based on a predefined general circuit model, which has not yet been reported. With CGs and this condition, we develop a heuristic synthesis algorithm which derives solutions similar to the state-graph approach while requiring significantly less CPU time
    Preview · Conference Paper · Feb 1997
  • [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionTubersSENs and SEGAsCell LineagemTOR Activation and Biallelic TSC Gene InactivationAlternative Signaling Cascades in TSC Brain LesionsStructural Alterations in Nontuber Brain AreasConclusions and Future DirectionsReferences
    No preview · Chapter · Jun 2010
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To elucidate the biological significance of fibroblast growth factor-2 (FGF-2) expression in epilepsy-associated malformations of cortical development, immunohistochemical expression of FGF-2 was investigated in the developing human cerebral mantles obtained from 30 autopsy cases of fetuses, stillborn infants and children ranging from 12 weeks gestation to 15 years old, and 70 surgically-resected corticectomy specimens from patients with medically intractable epilepsy, including: group I, 12 tubers of tuberous sclerosis; group II, 24 cases of focal cortical dysplasia (FCD) with balloon cells (BC); group III, 11 FCD without BC; group IV, 23 histologically normal-appearing neocortices from patients with Rasmussen encephalitis, cystic-gliotic encephalopathy, temporal lobe epilepsy; and group V, 14 normal-appearing neocortices adjacent to dysplastic lesions from groups I and II. FGF-2 expression was detected in a population of matrix cells and/or neuroblasts within the ventricular zone in fetuses younger than 19 weeks gestation. Nuclei of glioblasts and immature astrocytes were also positive for FGF-2 in cases older than 18 weeks gestation. FGF-2 expression was not detected in immature cortical plate neurons. Astrocytes and ependymal cells were positive for FGF-2 in the postnatal brains. Choroid plexus epithelium was strongly positive for FGF-2 in all cases examined. Among the corticectomy specimens, the cytoplasms and/or nuclei of dysmorphic neurons (DNs) and BCs in groups I and II were variably positive for FGF-2. The proportions of FGF-2 immunoreactive cells (FGF-2-IR%) was significantly higher in groups I (36.9 ± 9.6) and II (45.1 ± 7.0) than in groups III (21.0 ± 5.7), IV (14.4 ± 4.7) and V (24.3 ± 10.3), and that in group V was higher than in group IV (P<0.01). These results indicate that FGF-2 upregulation in DNs and BCs is an important feature common to groups I and II, and suggest that BCs and DNs in these groups represent disturbed gliogenesis from matrix cells and disturbed maturation of cortical neurons from migrating neuroblasts, respectively.
    Full-text · Article · Mar 2011 · Neuropathology
Show more