Vascular endothelial growth factor (
VEGF), a potent inducer of angiogenesis and vascular permeability in diverse physiological and pathological conditions, may be involved in the pathophysiology of
chronic subdural hematoma (CSDH). The present study investigated the source and mechanisms for the induction of
VEGF in CSDH by measuring the concentration of
VEGF in the
hematoma of 102 patients (122
hematomas) using the
enzyme-linked
immunosorbent assay technique. The relationship between the
VEGF concentration in
hematoma and the intrahematoma membranous structure confirmed by preoperative T(2)(*)-weighted magnetic resonance image was examined in 46 of these patients.
VEGF and
hypoxia-inducible factor-1alpha (HIF-1alpha) expression was immunohistochemically studied and microvessel density (MVD) in the outer membrane was identified using anti-CD31 antibody in 30 patients.
VEGF and HIF-1alpha were positive in the outer membranes of all 30 patients.
VEGF expression was significantly correlated to HIF-1alpha expression (r(s) = 0.651, p = 0.0084) and
VEGF concentration in the
hematoma (r(s) = 0.654, p = 0.0013).
VEGF concentration in layered
hematomas, which have intrahematoma membranous structure, was significantly higher than in non-layered
hematomas (p < 0.01). Although MVDs of the outer membranes were comparable to those described in
tumors, there was no significant relationship with
VEGF expression. The present study suggests that
VEGF in CSDH, which may be induced in the neomembrane by HIF-1 release, may give rise to the excessive development of fragile microvessels and hyperpermeability, resulting in the enlargement of CSDH.