Research ReportUpregulation of tissue inhibitor of metalloproteinase-1 contributes to restoration of the extracellular matrix in the rabbit basilar artery during cerebral vasospasm after subarachnoid hemorrhage

- This study investigated the mechanism of vascular remodeling after SAH.
- ECM components in the basilar artery were decreased in the early phase after SAH.
- After upregulation of TIMP-1, expression of ECM components recovered.
- Decreases in ECM components may facilitate vasoconstriction of the cerebral artery.
- TIMP-1 may play a protective role in cerebral vasospasm by repairing the ECM.

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.