Thrombin-induced TGF-β1 pathway: A cause of communicating hydrocephalus post subarachnoid hemorrhage

Abstract

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 cerebro-spinal fluid (CSF) in cerebral compartments during SAH. To investigate the mechanism of the communicating hydro-cephalus 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) inhib-itor, 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 subarach-noid meninges. TH-induced overexpression of TGF-β1 and activation of its downstream factors might be a mechanism of communicating hydrocephalus after SAH.