Involvement of Hypoxia-Inducible Factor-1.ALPHA. and Vascular Endothelial Growth Factor in the Mechanism of Development of Chronic Subdural Hematoma

Abstract

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-1a (HIF-1a) expression was immunohistochemically studied and microvessel density (MVD) in the outer membrane was identified using anti-CD31 antibody in 30 patients. VEGF and HIF-1a were positive in the outer membranes of all 30 patients. VEGF expression was significantly correlated to HIF-1a 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 º 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.

Resolution of Chronic Subdural Hematoma after Treatment with Tumor Necrosis Factor Alpha Inhibitor

“…These authors concluded that VEGF may be involved in the pathogenesis of cSDH. Others have reported similar findings [6]. Higher levels of IL-6 in cSDH fluid and higher levels of VEGF and bFGF in the membranes have been reported in recurrent cSDHs when compared with nonrecurrent collections [7].…”

Giant Cavernous Malformations in Young Adults: Report of two cases, Radiological Findings and Surgical Consequences

“…Imaging findings were highly suggestive for a giant cavernous malformation, after recent episode of hemorrhage. (10). The rate of bleeding is higher when the size of the lesion is greater than 10 mm and when the patient is aged 35 years or younger (11).…”

Apoptotic and anti-angiogenic effects of Pulsatilla�koreana extract on hepatocellular carcinoma

“…Recently, it has been reported that the angiogenic response increases during hepatocarcinogenesis, and targeting VEGF significantly attenuated HCC development and metastasis (19). HIF-1α is also known as a target regulator of angiogenesis along with VEGF in various types of cancers (20,21). Since inhibition of VEGF could be due to inactivation of HIF-1α, VEGF/ HIF-1α may provide a potential target for a novel therapeutic strategy against HCC.…”