title: Expression of Mitogen-Activated Protein Kinases in Chronic Subdural Hematoma Outer Membranes.
abstract: 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.
authors.affiliation: 1 Department of Neurological Surgery, Aichi Medical University , Aichi, Japan .
authors.forename: Masahiro
authors.initials: M
authors.lastname: Aoyama
authors.affiliation: 1 Department of Neurological Surgery, Aichi Medical University , Aichi, Japan .
authors.forename: Koji
authors.initials: K
authors.lastname: Osuka
authors.affiliation: 2 Department of Anatomy II, Fujita Health University School of Medicine , Aichi, Japan .
authors.forename: Nobuteru
authors.initials: N
authors.lastname: Usuda
authors.affiliation: 3 High Technology Research Center, Pharmacology, Showa Pharmaceutical University , Tokyo, Japan .
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: 1 Department of Neurological Surgery, Aichi Medical University , Aichi, Japan .
authors.forename: Reo
authors.initials: R
authors.lastname: Kawaguchi
authors.affiliation: 1 Department of Neurological Surgery, Aichi Medical University , Aichi, Japan .
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakura
authors.affiliation: 1 Department of Neurological Surgery, Aichi Medical University , Aichi, Japan .
authors.forename: Masakazu
authors.initials: M
authors.lastname: Takayasu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D020200:Hematoma, Subdural, Chronic / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D008578:Meninges / Q000378:metabolism*; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology; D014207:Trephining
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases
keywords: ERK; JNK; angiogenesis; chronic subdural hematoma; p38