Department of Neurology, First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, PR China.
Int J Mol Med. 2013 Mar;31(3):660-6. doi: 10.3892/ijmm.2013.1253. Epub 2013 Jan 22.
The mechanism of communicating hydrocephalus after subarachnoid hemorrhage (SAH) remains unclear. Revealing a signaling cascade may provide significant insights into the molecular etiology of the accumulation of cerebrospinal fluid (CSF) in cerebral compartments during SAH. To investigate the mechanism of the communicating hydrocephalus following SAH, we infused CSF with thrombin (TH), resulting in proinflammatory and proliferative responses in rat meninges of SAH. The effect of TH could be completely blocked by a transforming growth factor β1 (TGF-β1) inhibitor, SB-431542, suggesting that TH-stimulated proliferation of meninges is through the TGF-β1 signaling pathway. The cascade of TGF β1-Smad3 was significantly upregulated by TH, which, in turn, stimulated the proliferation of subarachnoid meninges. TH-induced overexpression of TGF-β1 and activation of its downstream factors might be a mechanism of communicating hydrocephalus after SAH.
蛛网膜下腔出血 (SAH) 后交通性脑积水的发病机制尚不清楚。揭示信号级联反应可能为蛛网膜下腔出血时脑脊液 (CSF) 在脑室内积聚的分子病因提供重要的见解。为了研究蛛网膜下腔出血后交通性脑积水的发病机制，我们向 CSF 中注入凝血酶 (TH)，导致 SAH 大鼠脑膜出现促炎和增殖反应。转化生长因子β1 (TGF-β1) 抑制剂 SB-431542 可完全阻断 TH 的作用，表明 TH 刺激脑膜增殖是通过 TGF-β1 信号通路。TH 显著上调 TGF-β1-Smad3 级联反应，进而刺激蛛网膜下腔脑膜增殖。TH 诱导的 TGF-β1 过度表达及其下游因子的激活可能是蛛网膜下腔出血后交通性脑积水的机制之一。
