The level of circulating endothelial progenitor cells may be associated with the occurrence and recurrence of chronic subdural hematoma

OBJECTIVES: The onset of chronic subdural hematoma may be associated with direct or indirect minor injuries to the head or a poorly repaired vascular injury. Endothelial progenitor cells happen to be one of the key factors involved in hemostasis and vascular repair. This study was designed to observe the levels of endothelial progenitor cells, white blood cells, platelets, and other indicators in the peripheral blood of patients diagnosed with chronic subdural hematoma to determine the possible relationship between the endothelial progenitor cells and the occurrence, development, and outcomes of chronic subdural hematoma. METHOD: We enrolled 30 patients with diagnosed chronic subdural hematoma by computer tomography scanning and operating procedure at Tianjin Medical University General Hospital from July 2009 to July 2011. Meanwhile, we collected 30 cases of peripheral blood samples from healthy volunteers over the age of 50. Approximately 2 ml of blood was taken from veins of the elbow to test the peripheral blood routine and coagulation function. The content of endothelial progenitor cells in peripheral blood mononuclear cells was determined by flow cytometry. RESULTS: The level of endothelial progenitor cells in peripheral blood was significantly lower in preoperational patients with chronic subdural hematomas than in controls. There were no significant differences between the two groups regarding the blood routine and coagulation function. However, the levels of circulating endothelial progenitor cells were significantly different between the recurrent group and the non-recurrent group. CONCLUSIONS: The level of circulating endothelial progenitor cells in chronic subdural hematoma patients was significantly lower than the level in healthy controls. Meanwhile, the level of endothelial progenitor cells in recurrent patients was significantly lower than the level in patients without recurrence. Endothelial progenitor cells may ...

Blockade of the Sonic Hedgehog Signalling Pathway Inhibits Choroidal Neovascularization in a Laser-induced Rat Model / 华中科技大学学报（医学）（英德文版）

Sonic hedgehog (Shh) signaling has recently been shown to be involved in the pathological angiogenesis in response to tissue hypoxia and ischemic injury. Hypoxia/ischemia is considered to play an important role in the development of choroidal neovascularization (CNV). This study was aimed to examine the effect of blockade of the Shh signaling pathway on CNV and the underlying mechanism. A total of 64 male Brown-Norway (BN) rats were used in this study. One eye of each rat underwent laser photocoagulation. The other eye served as normal control. After the laser treatment,the 64 rats were divided into four groups (n=16 in each group): Blank control group, in which no intravitreal administration was given; cyclopamine group, recombinant Shh N-terminals protein (rShh)group and phosphate-buffered saline (PBS) group, in which cyclopamine (a Shh inhibitor), rShh (a Shh activator) and PBS were intravitreally injected into the laser-treated eyes respectively every other day for a total of four intravitreal injections immediately after the laser treatment. Fourteen days after the intravitreal administration, the changes of CNV-related variables, including positive CNV lesion percentage, CNV membrane area and CNV membrane thickness, were evaluated by fluorescein angiography, indocyanine green angiography and pathological examinations. The mRNA and protein expression of PTCH1, Glil, HIF-la, VEGF and DLL4 in each group on 14 days of CNV model was detected by real-time quantitative PCR and western blot analysis, and the relationship between the Shh cascade and the HIF-1 α-VEGF-DLL4 cascade in CNV was analyzed. The results showed that the CNV membrane area and the CNV membrane thickness were decreased by 62.5% and 41.9% in the cyclopamine group and increased by 85.7% and 64.3% in the rShh group in comparison to those in the blank control group (P＜0.01 for each). There was no significant difference in the CNV membrane area and thickness between the blank control group and PBS group (P=0.102 and P=0.063, respectively). Real-time quantitative PCR revealed a 5.23-, 4.14-, 2.97-, 2.78- and 2.39-fold up-regulation of the mRNA expression of PTCH1, Glil, HIF-la, VEGF and DLL4 genes in the laser-treated eyes compared with the normal control eyes in the control group. In the cyclopamine group, the mRNA and protein expression of Glil, HIF-lα, VEGF and DLL4 was significantly down-regulated (P＜0.05 for each) while the expression of PTCH1 showed no significant changes at the mRNA (P=0.293) and protein level (P=0.304). The mRNA expression and protein expression (P=0.001 and P=0.021, respectively) of PTCH1, Glil, HIF-lα, VEGF and DLL4 was significantly increased in the rShh group when compared with the control group. The expression level of these genes was related to the severity of the CNV. It was concluded that intravitreal administration of cyclopamine can effectively inhibit the formation of laser-induced experimental CNV by down-regulating the expression of the HIF-la-VEGF-DLL4 cascade in CNV. The Shh signaling pathway as an upstream signaling pathway of HIF-1 a-VEGF-DLL4 cascade is implicated in the development of experimental CNV.