Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5685000 | Translational Research | 2017 | 16 Pages |
Abstract
Fibrosis of the subarachnoid space (SAS) after infection, inflammation, or hemorrhage can impair cerebrospinal fluid absorption and circulation, causing diffuse ventricular dilatation. In the present study, we tested the hypothesis that urokinase (also known as urokinase-type plasminogen activator [uPA]), a fibrinolytic agent, attenuates fibrosis and ventriculomegaly in a rat model of kaolin-induced communicating hydrocephalus and thus may have potential as a therapy for these conditions. Thirty microliters of sterile 25% kaolin suspension was injected into the basal cisterns of adult Sprague-Dawley rats to induce hydrocephalus, and 2 intraventricular injections of either uPA or vehicle (saline) were administered immediately and 3 days thereafter. Ventricular volumes were measured by magnetic resonance imaging (MRI) on days 3, 14, and 28 after kaolin injection. Fibrosis and reactive astrogliosis were evaluated on day 28 by immunofluorescence and Western blotting. Neurocognitive features were tested using the Morris water maze from days 23 to 28. MRI analysis demonstrated that kaolin administration successfully induced hydrocephalus in rats and that uPA treatment significantly attenuated ventricular enlargement. In addition, uPA inhibited the deposition of laminin and fibronectin, extracellular matrix molecules, in the SAS, attenuated gliosis, and improved learning and memory in kaolin-treated rats. Therefore, we concluded that uPA prevents the development of kaolin-induced communicating hydrocephalus by preventing the development of subarachnoid fibrosis and by eliciting improvements in neurocognition. The results of this study indicate that uPA may be a novel clinical therapy for communicating hydrocephalus.
Keywords
ECMPBSGFAPBVStPAGAPDHPLGuPAuPARSASMRIImmunofluorescencelateral ventriclethird ventricleMagnetic resonance imagingBlood vesselsSubarachnoid spaceTissue-type plasminogen activatorurokinase-type plasminogen activatorExtracellular matrixCSFCerebrospinal fluidphosphate-buffered solutionWestern blotGlial fibrillary acidic proteinPlasminPlasminogenglyceraldehyde-3-phosphate dehydrogenaseUrokinase-type plasminogen activator receptor
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Authors
Zhou Feng, Qiang Tan, Jun Tang, Lin Li, Yihao Tao, Yujie Chen, Yunfeng Yang, Chunxia Luo, Hua Feng, Gang Zhu, Qianwei Chen, Zhi Chen,