Growth factors and inflammatory
cytokines activate the
mitogen-activated protein kinase (MAPK) cascade. Previous studies have shown that
chronic subdural hematoma (CSDH) fluid contains these factors and
cytokines. In this study, expression of three major MAPK cascade transmitters in the outer membrane of CSDH was assessed. Eleven patients whose outer membrane and CSDH fluid were successfully obtained during
trepanation surgery were included in this study. Expression of
extracellular signal-regulated kinase (ERK), phosphorylated (p)-ERK, p38, p-p38,
c-Jun N-terminal kinase (JNK), p-JNK, and actin was examined by Western blot and immunostaining. We examined whether CSDH fluid could activate MAPKs in cultured endothelial cells (ECs) or fibroblasts in vitro. Western blot analysis showed that p-ERK was present in all samples, whereas p-p38 and p-JNK were detected, but not in all cases. Immunostaining showed that all three p-MAPKs were expressed in vascular endothelium. However, only p-ERK was expressed in fibroblasts. Expression of p-
extracellular signal-regulated kinase kinase (MEK) and p-ERK in ECs and fibroblasts was significantly induced immediately
after treatment with CSDH fluid, whereas p-p38 and p-JNK expression was significantly induced in ECs 60 min
after treatment, but not in fibroblasts. Activation of
MEK was significantly inhibited by treatment with
antibodies directed against
interleukin-6 and
vascular endothelial growth factor in ECs, but not in fibroblasts. Inflammatory
cytokines and
growth factors in CSDH fluids might activate major MAPKs in ECs, which might be associated with neovascularization in the outer membrane of CSDH. These MAPK pathways could become novel targets for treatment of CSDHs.