Link Between Receptors That Engage in Developing Vasospasm After Subarachnoid Hemorrhage in Mice
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.
KeywordsEpidermal growth factor receptor Toll-like receptor 4 Tenascin-C Cerebral vasospasm
This work was supported in part by a grant-in-aid for Scientific Research from Japan Society for the Promotion of Science to Drs. Shiba and Suzuki. We thank Chiduru Yamamoto (Department of Neurosurgery, Mie University Graduate School of Medicine) for her assistance.
Conflict of Interest: The authors declare that they have no conflict of interest.
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