Upregulation of tissue inhibitor of metalloproteinase-1 contributes to restoration of the extracellular matrix in the rabbit basilar artery during cerebral vasospasm after subarachnoid hemorrhage.
Vascular remodeling caused by extracellular matrix (ECM) metabolism contributes to the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). The balance between tissue inhibitor of metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) plays an important role in ECM remodeling. We investigated the mechanism of vascular remodeling following cerebral vasospasm in a rabbit double hemorrhage model. Rabbit basilar arteries were harvested on days 3, 5, and 7 after initial hemorrhage. TIMP-1, TIMP-2, MMP-2, and MMP-9 mRNA and protein expression were investigated with microarray analysis, quantitative real-time PCR, immunoblot analysis, and enzyme-linked immunosorbent assay (ELISA). The expression and localization of TIMP-1, TIMP-2, MMP-2, MMP-9, elastin, fibronectin, laminin, and collagens I, III, and IV were investigated with immuohistochemical staining. After SAH, TIMP-1 mRNA and protein expression were significantly increased on day 3 and then decreased to the control level on days 5 and 7. MMP-9 protein expression was significantly increased on day 7. TIMP-2 and MMP-2 mRNA and protein expression were significantly increased on day 7. Elastin, fibronectin, laminin, and collagens I, III, and IV protein expression was decreased on day 3 and then restored to control levels on day 7. Upregulation of TIMP-1 during the early phase of cerebral vasospasm may contribute to the recovery of the ECM during the late phase of cerebral vasospasm, resulting in a protective role of TIMP-1 from cerebral vasospasm. Moreover, the increase in arterial compliance by the decrease in ECM during the early phase of cerebral vasospasm may facilitate vasoconstriction of the cerebral artery.
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, Fukuoka, Japan.
Ryota
R
Kurogi
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, Fukuoka, Japan; Department of Cerebrovascular Surgery, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka City 350-1298, Saitama, Japan. Electronic address: ykikkawa@saitama-med.ac.jp.
Yuichiro
Y
Kikkawa
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, Fukuoka, Japan.
Satoshi
S
Matsuo
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, Fukuoka, Japan; Department of Neurosurgery, Steel Memorial Yawata Hospital, 1-1-1 Harunomachi, Yahatahigashi-ku, Kitakyusyu City 805-8508, Fukuoka, Japan.
Akira
A
Nakamizo
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, Fukuoka, Japan.
Masahiro
M
Mizoguchi
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, Fukuoka, Japan.
Tomio
T
Sasaki
D000818:Animals; D001488:Basilar Artery / Q000378:metabolism*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000473:pathology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*; D020301:Vasospasm, Intracranial / Q000209:etiology* / Q000473:pathology*
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1
Cerebral vasospasm; Extracellular matrix; Matrix metalloproteinase; Subarachnoid hemorrhage; Tissue inhibitor of metalloproteinase; Vascular remodeling