Platelet-derived Growth Factor Activates Pericytes in the Microvessels of Chronic Subdural Hematoma Outer Membranes

Abstract

Angiogenesis is one of the growth mechanisms of chronic subdural hematoma (CSDH). Pericytes have been implicated in the capillary sprouting during angiogenesis and are involved in brain ischemia and diabetic retinopathy. This study examined the pericyte expressions in CSDH outer membranes obtained during trepanation surgery. Eight samples of CSDH outer membranes and 35 samples of CSDH fluid were included. NG2, N-cadherin, VE-cadherin, Tie-2, endothelial nitric oxide synthase (eNOS), platelet-derived growth factor (PDGF) receptor-β (PDGFR-β), a well-known marker of pericytes, phosphorylated PDGFR-β at Tyr751, and β-actin expressions, were examined using western blot analysis. PDGFR-β, N-cadherin, and Tie-2 expression levels were also examined using immunohistochemistry. The concentrations of PDGF-BB in CSDH fluid samples were measured using enzyme-linked immunosorbent assay kits. NG2, N-cadherin, VE-cadherin, Tie-2, eNOS, PDGFR-β, and eNOS expressions in CSDH outer membranes were confirmed in all cases. Furthermore, phosphorylated PDGFR-β at Tyr751 was also detected. In addition, PDGFR-β, N-cadherin, and Tie-2 expressions were localized to the endothelial cells of the vessels within CSDH outer membranes by immunohistochemistry. The concentration of PDGF-BB in CSDH fluids was significantly higher than that in cerebrospinal fluid. These findings indicate that PDGF activates pericytes in the microvessels of CSDH outer membranes and suggest that pericytes are crucial in CSDH angiogenesis through the PDGF/PDGFR-β signaling pathway.

Keywords

• angiogenesis
• chronic subdural hematoma
• n-cadherin
• pericyte
• platelet-derived growth factor receptor β