title: Effects of Tenascin-C Knockout on Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage in Mice.
abstract: A matricellular protein tenascin-C (TNC) has been suggested to play a role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH), but the direct evidence remains lacking. In this study, we examined effects of TNC knockout (TNKO) on cerebral vasospasm after experimental SAH in mice. C57BL/6 wild-type (WT) or TNKO mice were subjected to SAH by endovascular puncture. Ten WT and ten TNKO mice were randomized to WT sham (n = 4), TNKO sham (n = 4), WT SAH (n = 6), and TNKO SAH (n = 6) groups. In addition to neurobehavioral impairments and severity of SAH, cerebral vasospasm was assessed by morphometric measurements of the left internal carotid artery (ICA). Infiltration of inflammatory cells in the subarachnoid periarterial space was also assessed, and expressions of TNC and mitogen-activated protein kinases (MAPKs) in the ICA were immunohistochemically evaluated at 24 h post-surgery. TNC was induced in the smooth muscle cell layers and the adventitia in the spastic ICAs as well as the periarterial inflammatory cells in WT SAH mice. Compared with WT SAH mice, TNKO SAH mice showed better neurological scores and less severe cerebral vasospasm, as well as fewer inflammatory cell infiltration in the periarterial space. Post-SAH activation of MAPKs in the smooth muscle cell layers of the ICAs was also prevented in TNKO SAH mice. The findings in the present study suggest that TNC causes the development of cerebral vasospasm via pro-inflammatory effects and activation of MAPKs.
authors.affiliation: Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Shiba
authors.affiliation: Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Kawakita
authors.affiliation: Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Shimojo
authors.affiliation: Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.|Research Center for Matrix Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Imanaka-Yoshida
authors.affiliation: Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.|Research Center for Matrix Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan. suzuki02@clin.medic.mie-u.ac.jp.|Research Center for Matrix Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan. suzuki02@clin.medic.mie-u.ac.jp.
authors.forename: Hidenori
authors.identifier: http://orcid.org/0000-0002-8555-5448
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013345:Subarachnoid Hemorrhage / Q000235:genetics / Q000378:metabolism*; D019063:Tenascin / Q000172:deficiency* / Q000235:genetics; D020301:Vasospasm, Intracranial / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*
chemical_list: D019063:Tenascin
keywords: Cerebral vasospasm; Mitogen-activated protein kinase; Subarachnoid hemorrhage; Tenascin-C