VEGF/VEGFR-2 changes in frontal cortex, choroid plexus, and CSF after chronic obstructive hydrocephalus.

VEGF/VEGFR-2 changes in frontal cortex, choroid plexus, and CSF after chronic obstructive hydrocephalus.
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DOI:
10.1016/j.jns.2010.06.012
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发表时间:
2010-09-15
影响因子:
4.4
通讯作者:
Luciano, Mark G.
Luciano, Mark G.
中科院分区:
医学3区
文献类型:
--
作者:
Yang, Jun;Dombrowski, Stephen M.;Deshpande, Abhishek;Krajcir, Natalie;Luciano, Mark G.

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慢性脑积水(CH)通常与脑血流量(CBF)和血氧水平降低有关。虽然确切的病理生理机制尚不清楚,但可能与血管内皮生长因子及其受体-2(VEGFR-2)有关。由于脉络丛(CP)参与脑脊液(CSF)的产生,并分泌包括VEGF在内的多种生长因子,因此了解CP-CSF循环系统中VEGF/VEGFR-2的水平非常重要。结果显示,与SC组相比,CH组大鼠额叶皮质(FC)CBF和VEGFR-2水平显著降低,而VEGF水平无明显变化。FC患者脑血流量变化与VEGFR-2水平呈正相关(P=0.024)。免疫组织化学(IHC)显示血管内皮生长因子/VEGFR-2在CP组织中呈强阳性表达。CH诱导后,脑室脑脊液容量和血管内皮细胞生长因子水平显著增加。这些结果提示,FC中VEGFR-2水平的降低可能与脑血流量的减少有关,而脑脊液中VEGF水平的升高可能反映了脑脊液出口阻断后脑脊液分泌的血管内皮生长因子的低氧反应和/或积聚。进一步研究脑脊液中不同部位的血管内皮生长因子水平可能有助于更好地了解正常脑和脑积水中血管内皮生长因子受体-2的调控机制,并可能为脑积水的潜在治疗方案提供一种可行的途径。
Chronic Hydrocephalus (CH) is often associated with decreased cerebral blood flow (CBF) and oxygen levels. While the exact pathophysiology is not clear, vascular endothelial growth factor (VEGF) and its receptor-2 (VEGFR-2) may be involved. Because the choroid plexus (CP) is involved in cerebrospinal fluid (CSF) production and secretes numerous growth factors including VEGF, it is important to understand VEGF/VEGFR-2 levels in the CP–CSF circulatory system. Our results showed significant decreases in CBF and VEGFR-2 levels in frontal cortex (FC) in CH compared with SC; there were no significant changes in VEGF levels. CBF change in FC was positively correlated with VEGFR-2 levels (P=0.024). Immunohistochemistry (IHC) showed robust expression of VEGF/VEGFR-2 in CP. After CH induction, ventricular CSF volume and VEGF levels significantly increased. These results suggest that the decreased VEGFR-2 levels in FC may be contributed to decreased CBF and increased ventricular CSF-VEGF levels possibly reflected a hypoxic response and/or accumulation of VEGF from CP secretion after blockage of CSF outlet. Further investigation into CSF-VEGF levels in different sites may provide a better understanding of VEGF/VEGFR-2 modulation in the normal and hydrocephalic brain, and may represent a feasible approach to potential therapeutic options for hydrocephalus.
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