Heep Axel, Stoffel-Wagner Birgit, Bartmann Peter, Benseler Susanne, Schaller Carlo, Groneck Peter, Obladen Michael, Felderhoff-Mueser Ursula
Department of Neonatology, University of Bonn, Adenauerallee 119, D-53113 Bonn, Germany.
Pediatr Res. 2004 Nov;56(5):768-74. doi: 10.1203/01.PDR.0000141524.32142.53. Epub 2004 Aug 19.
The expression of specific growth factors such as vascular endothelial growth factor (VEGF) and transforming growth factor-beta1 (TGF-beta1) is of importance during brain development and in the pathogenesis of neurodegenerative disorders. VEGF and TGF-beta1 was studied in the cerebrospinal fluid (CSF) of neonates with posthemorrhagic hydrocephalus (PHHC) and nonhemorrhagic hydrocephalus. For determining the interference of inflammatory cytokine interaction with the expression of VEGF and TGF-beta1, IL-6 and IL-10 CSF concentrations were measured. Eighteen neonates who had PHHC and underwent serial reservoir puncture and nine neonates who had congenital nonhemorrhagic hydrocephalus (CHC) and underwent first shunt surgery were included in the study. CSF samples of 11 neonates with lumbar puncture for the exclusion of meningitis served as control subjects. VEGF, TGF-beta1, IL-6, and IL-10 concentrations in the CSF were measured by ELISA technique. VEGF concentrations in the CSF of patients with PHHC were significantly higher (median: 377 pg/mL; range: 101-1301 pg/mL) when compared with patients with CHC (median: 66 pg/mL; range: 3-1991; p < 0.001) and control subjects (median: 2 pg/mL; range: 0-12 pg/mL; p < 0.0001). TGF-beta1 CSF concentrations did not differ from control infants in all groups. Median IL-6 and IL-10 concentrations in the CSF were found to be low in all patient groups. Increased release of VEGF in the CSF of neonates with PHHC and nonhemorrhagic hydrocephalus may serve as an indicator of brain injury from progressive ventricular dilation. TGF-beta1 CSF concentrations are not elevated in the phase of acute fibroproliferative reactions in patients with PHHC.
血管内皮生长因子(VEGF)和转化生长因子-β1(TGF-β1)等特定生长因子的表达在脑发育过程以及神经退行性疾病的发病机制中具有重要意义。本研究对出血后脑积水(PHHC)和非出血性脑积水新生儿的脑脊液(CSF)中的VEGF和TGF-β1进行了研究。为了确定炎性细胞因子相互作用对VEGF和TGF-β1表达的干扰,检测了CSF中IL-6和IL-10的浓度。本研究纳入了18例患有PHHC并接受系列储液囊穿刺的新生儿以及9例患有先天性非出血性脑积水(CHC)并接受首次分流手术的新生儿。11例因腰椎穿刺排除脑膜炎的新生儿的CSF样本作为对照。采用ELISA技术检测CSF中VEGF、TGF-β1、IL-6和IL-10的浓度。与CHC患者(中位数:66 pg/mL;范围:3 - 1991;p < 0.001)和对照受试者(中位数:2 pg/mL;范围:0 - 12 pg/mL;p < 0.0001)相比,PHHC患者CSF中的VEGF浓度显著更高(中位数:377 pg/mL;范围:101 - 1301 pg/mL)。所有组中TGF-β1的CSF浓度与对照婴儿无差异。所有患者组CSF中的IL-6和IL-10中位数浓度均较低。PHHC和非出血性脑积水新生儿CSF中VEGF释放增加可能是进行性脑室扩张导致脑损伤的一个指标。PHHC患者急性纤维增生反应阶段CSF中的TGF-β1浓度并未升高。