The role of rosiglitazone in the proliferation of vascular smooth muscle cells after experimental subarachnoid hemorrhage.

BACKGROUND: Recent evidence has demonstrated that rosiglitazone can attenuate cerebral vasospasm following subarachnoid hemorrhage (SAH). Some studies have shown that rosiglitazone can suppress inflammation and immune responses after SAH. However, the precise molecular mechanisms by which cerebral vasospasm is attenuated is not clear. METHODS: In this study, SAH was created using a "double hemorrhage" injection rat model. Rats were randomly divided into three groups and treated with saline (control group), untreated (SAH group), or treated with rosiglitazone. Using immunocytochemistry, hematoxylin and eosin (HE) staining, and measurement of the basilar artery, we investigated the formation of pathologic changes in the basilar artery, measured the expression of caveolin-1 and proliferating cell nuclear antigen (PCNA), and investigated the role of rosiglitazone in vascular smooth muscle cell (VSMC) proliferation in the basilar artery after SAH. RESULTS: In this study, we observed significant pathologic changes in the basilar artery after experimental SAH. The level of vasospasm gradually increased with time during the 1st week, peaked on day 7, and almost recovered on day 14. After rosiglitazone treatment, the level of vasospasm was significantly attenuated in comparison with the SAH group. Immunocytochemistry staining showed that caveolin-1 expression was significantly increased in the rosiglitazone group, compared with the SAH group. Inversely, the expression of PCNA showed a notable decrease after rosiglitazone treatment. CONCLUSIONS: The results indicate that rosiglitazone can attenuate cerebral vasospasm following SAH. Up-regulation of caveolin-1 by rosiglitazone may be a new molecular mechanism for this response, which is to inhibit proliferation of VSMCs after SAH, and this study may provide a novel insight to prevent delayed cerebral vasospasm (DCVS).

Dynamic expression of the suppressor of cytokine signaling-3 and cytokines in the cerebral basilar artery of rats with subarachnoid hemorrhage, and the effect of acetylcholine.

BACKGROUND: There are complex interactions between acetylcholine (ACh), the suppressor of cytokine signaling-3 (SOCS-3), and cytokines, however, little is known about their dynamic expression or their effects on cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). Therefore, we aimed to describe and clarify the dynamic expression of SOCS-3 and cytokines after SAH, as well as the relationships between the levels of SOCS-3, cytokines, and ACh. METHODS: The rat model of single cisterna magna injection was used to mimic acute SAH. The degree of CVS was indicated by lumen diameter and artery wall thickness under H&E staining. A semi-quantitative immunohistochemical analysis method was used to clarify the role of SOCS-3 in the CVS after SAH. We also measured the content of IL-6 and IL-10 in cerebrospinal fluid. RESULTS: We found that SOCS-3 expression levels increased rapidly within 12 h after SAH, more slowly after 12 h, and did not reach a peak within 48 h. Interleukin 6 (IL-6) levels rapidly increased within 24 h after SAH, reached a peak 24 h after SAH, and decreased slightly at 48 h. IL-10 levels increased during the first 6 h after SAH, after which this increase tapered off. ACh treatment reduced IL-6 levels and resulted in elevated levels of SOCS-3, but had no effect on IL-10 expression. Furthermore, ACh treatment relieved basilar arterial vasospasm, whereas mecamylamine pretreatment counteracted the activity of ACh. CONCLUSIONS: Taken together, these data indicate that SOCS-3 was involved in vasospasm via an IL-6- and IL-10-related mechanism, and that CVS following SAH could be reversed by the intraventricular injection of ACh.