Activation of Ras/MEK/ERK signaling in chronic subdural hematoma outer membranes

Abstract

Chronic subdural hematoma (CSDH) is considered to be an angiogenic disease. Vascular endothelial growth factor (VEGF), one of the important growth factors regulating angiogenesis, is expressed in the neomembranes and also in hematoma fluid, and the Ras/MEK/ERK signaling pathway has been implicated in angiogenesis by VEGF. In the present study, the status of this signaling pathway in CSDH outer membranes was examined using outer membranes obtained during trepanation surgery. The expression levels of Ras, Ras-GAP, c-Raf, MEK, ERK, phosphorylated (p)-ERK, endothelial nitric oxide synthase (eNOS) and actin were examined by western blot analysis; the expression of p-ERK was also examined by immunohistochemistry. Ras, Ras-GAP, c-Raf, MEK, ERK and eNOS were detected in all cases. In addition, the expression of p-ERK was confirmed in all cases, and p-ERK was localized to the endothelial cells of the vessels in CSDH outer membranes. These findings indicated that Ras/MEK/ERK signaling is activated in the CSDH outer membranes and suggested the possibility that the Ras/MEK/ERK pathway might be activated by VEGF and play a critical role in the angiogenesis of CSDHs.