Nakano Fumi, Kawakita Fumihiro, Liu Lei, Nakatsuka Yoshinari, Nishikawa Hirofumi, Okada Takeshi, Shiba Masato, Suzuki Hidenori
Department of Neurosurgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Acta Neurochir Suppl. 2020;127:55-58. doi: 10.1007/978-3-030-04615-6_9.
Vasospasm after subarachnoid hemorrhage (SAH) has been studied, but the mechanisms remain to be unveiled. Tenascin-C (TNC), which is a matricellular protein and reported to increase in spastic cerebral artery wall after SAH, is a ligand for both Toll-like receptor 4 (TLR4) and epidermal growth factor receptor (EGFR). Our previous studies suggested the involvement of TNC and these receptors in vasoconstriction or vasospasm after SAH. In this study, we investigated whether upregulation of TNC and TLR4 is observed and if an EGFR inhibitor has suppressive effects against them in a mice endovascular perforation SAH model. At 24 h after SAH, TNC and TLR4 expressions were widely observed in spastic cerebral arteries, and these expressions were suppressed by the administration of an EGFR inhibitor. From these results, EGFR inhibitors possibly suppress the expression of not only EGFR but also TLR4 at least partly through regulating TNC upregulation. More studies are needed to clarify the precise mechanisms linking these receptors.
蛛网膜下腔出血（SAH）后的血管痉挛已得到研究，但其机制仍有待揭示。腱生蛋白-C（TNC）是一种基质细胞蛋白，据报道在SAH后痉挛性脑动脉壁中会增加，它是Toll样受体4（TLR4）和表皮生长因子受体（EGFR）的配体。我们之前的研究表明TNC和这些受体参与了SAH后的血管收缩或血管痉挛。在本研究中，我们调查了在小鼠血管内穿刺SAH模型中是否观察到TNC和TLR4的上调，以及EGFR抑制剂是否对它们有抑制作用。SAH后24小时，在痉挛性脑动脉中广泛观察到TNC和TLR4的表达，并且这些表达通过给予EGFR抑制剂而受到抑制。从这些结果来看，EGFR抑制剂可能至少部分地通过调节TNC上调来抑制EGFR和TLR4的表达。需要更多研究来阐明这些受体之间联系的精确机制。
