Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China.
J Neurol Sci. 2011 Jun 15;305(1-2):85-91. doi: 10.1016/j.jns.2011.03.006. Epub 2011 Mar 26.
The pathogenesis of cerebral vasospasm is closely associated with inflammation and immune response in arterial walls. Recently, the authors proved the key role of Toll-like receptor (TLR)4 in the development of vasospasm in experimental subarachnoid hemorrhage (SAH) model. Because peroxisome proliferator-activated receptor (PPAR) gamma agonists are identified as effective inhibitors of TLR4 activation, we investigated the anti-inflammation properties of PPAR-gamma agonist rosiglitazone in basilar arteries in a rat experimental SAH model and evaluated the effects of rosiglitazone on vasospasm. Inflammatory responses in basilar arteries were assessed by immunohistochemical staining for intercellular molecule (ICAM)-1 and myeloperoxidase (MPO). Expression of TLR4 was determined by western blot analysis. The degree of cerebral vasospasm was evaluated by measuring the mean diameter and cross-sectional area of basilar arteries. Rosiglitazone suppressed the SAH-induced inflammatory responses in basilar arteries by inhibiting the TLR4 signalling. Furthermore, rosiglitazone could attenuate cerebral vasospasm following SAH. Therefore, we suggested that PPAR-gamma agonists may be potential therapeutic agents for cerebral vasospasm.
脑血管痉挛的发病机制与动脉壁的炎症和免疫反应密切相关。最近，作者证明了 Toll 样受体（TLR）4 在蛛网膜下腔出血（SAH）模型中血管痉挛发展中的关键作用。由于过氧化物酶体增殖物激活受体（PPAR）γ激动剂被确定为 TLR4 激活的有效抑制剂，我们研究了 PPAR-γ激动剂罗格列酮在大鼠实验性 SAH 模型基底动脉中的抗炎特性，并评估了罗格列酮对血管痉挛的影响。通过免疫组织化学染色法检测细胞间分子（ICAM）-1 和髓过氧化物酶（MPO）评估基底动脉中的炎症反应。通过 Western blot 分析确定 TLR4 的表达。通过测量基底动脉的平均直径和截面积来评估脑动脉痉挛的程度。罗格列酮通过抑制 TLR4 信号通路抑制 SAH 诱导的基底动脉炎症反应。此外，罗格列酮可减轻 SAH 后的脑血管痉挛。因此，我们认为 PPAR-γ激动剂可能是治疗脑血管痉挛的潜在治疗药物。
