title: Cellular distribution of vascular endothelial growth factor A (VEGFA) and B (VEGFB) and VEGF receptors 1 and 2 in focal cortical dysplasia type IIB.
abstract: Members of the vascular endothelial growth factor (VEGF) family are key signaling proteins in the induction and regulation of angiogenesis, both during development and in pathological conditions. However, signaling mediated through VEGF family proteins and their receptors has recently been shown to have direct effects on neurons and glial cells. In the present study, we immunocytochemically investigated the expression and cellular distribution of VEGFA, VEGFB, and their associated receptors (VEGFR-1 and VEGFR-2) in focal cortical dysplasia (FCD) type IIB from patients with medically intractable epilepsy. Histologically normal temporal cortex and perilesional regions displayed neuronal immunoreactivity (IR) for VEGFA, VEGFB, and VEGF receptors (VEGFR-1 and VEGFR-2), mainly in pyramidal neurons. Weak IR was observed in blood vessels and there was no notable glial IR within the grey and white matter. In all FCD specimens, VEGFA, VEGFB, and both VEGF receptors were highly expressed in dysplastic neurons. IR in astroglial and balloon cells was observed for VEGFA and its receptors. VEGFR-1 displayed strong endothelial staining in FCD. Double-labeling also showed expression of VEGFA, VEGFB and VEGFR-1 in cells of the microglia/macrophage lineage. The neuronal expression of both VEGFA and VEGFB, together with their specific receptors in FCD, suggests autocrine/paracrine effects on dysplastic neurons. These autocrine/paracrine effects could play a role in the development of FCD, preventing the death of abnormal neuronal cells. In addition, the expression of VEGFA and its receptors in glial cells within the dysplastic cortex indicates that VEGF-mediated signaling could contribute to astroglial activation and associated inflammatory reactions.
authors.affiliation: Department of (Neuro) Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Karin
authors.initials: K
authors.lastname: Boer
authors.forename: Dirk
authors.initials: D
authors.lastname: Troost
authors.forename: Wim G M
authors.initials: WG
authors.lastname: Spliet
authors.forename: Peter C
authors.initials: PC
authors.lastname: van Rijen
authors.forename: Jan A
authors.initials: JA
authors.lastname: Gorter
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002648:Child; D004827:Epilepsy / Q000150:complications; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D054220:Malformations of Cortical Development / Q000145:classification / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D042561:Vascular Endothelial Growth Factor B / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D016900:Neurofilament Proteins; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C489788:MAP2 protein, human; C467484:VEGFA protein, human; C467485:VEGFB protein, human