title: Activation of PI3 kinase/Akt signaling in chronic subdural hematoma outer membranes.
abstract: Chronic subdural hematoma (CSDH) is an angiogenic disease that is recognized as a cause of treatable dementia with unknown pathogenesis. Vascular endothelial growth factor (VEGF), a potent growth factor regulating angiogenesis through the phosphatidylinositol 3-kinase (PI3-kinase)/Akt pathway, has been implicated in its etiology. The status of this signaling pathway in CSDH outer membranes was examined in the present study, using outer membranes obtained during trepanation surgery. Expressions of PI3-kinase, PKB-kinase, Akt, phosphorylated Akt at Ser(473) (p-Akt), endothelial nitric oxide synthase (eNOS), vascular endothelial-cadherin (VE-cadherin), and actin were examined by Western blot analysis, together with their immunohistochemistry. PI3-kinase, Akt, eNOS, and VE-cadherin were detected in all cases. The magnitude of the expression of p-Akt varied among cases; however, the localization was revealed to be present in endothelial cells of vessels in CSDH outer membranes, together with VEGF and VE-cadherin detected in endothelial cells of vessels. These findings suggest that the PI3-kinase/Akt signaling is activated in CSDH outer membranes, and indicate the possibility that the PI3 kinase/Akt pathway might be activated by VEGF and play a critical role in the angiogenesis of CSDH.
authors.affiliation: Department of Neurological Surgery, Aichi Medical University, Nagakute, Aichi-gun, Japan.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Funai
authors.forename: Koji
authors.initials: K
authors.lastname: Osuka
authors.forename: Nobuteru
authors.initials: N
authors.lastname: Usuda
authors.forename: Kimie
authors.initials: K
authors.lastname: Atsuzawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Inukai
authors.forename: Muneyoshi
authors.initials: M
authors.lastname: Yasuda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Masakazu
authors.initials: M
authors.lastname: Takayasu
mesh_terms: D000368:Aged; D005260:Female; D020200:Hematoma, Subdural, Chronic / Q000201:enzymology / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D008297:Male; D008578:Meninges / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism*; D008875:Middle Aged; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism* / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt