Abstract WP298: Matrix Metalloproteinases Are Involved In The Regulation Of Angiogenesis After Intracerebral Hemorrhage

Background and purpose: Intracerebral hemorrhage (ICH) is one of the most devastating subtypes of stroke. And our previous work has demonstrated that ICH induces angiogenesis, accompanied by up-regulation of pro-angiogenic factors. Matrix metalloproteinases (MMPs) can cause blood-brain barrier dysfunction by degrading the extracellular cellular matrix (ECM) around the vessels after ICH, but opening a way for the prolonging newborn vessels is a key step for their functional structure, therefore, the purpose of the study is to investigate whether MMPs are involved in the process of angiogenesis after ICH. Methods: Thirty Kunming mice were randomly divided into sham group, ICH group and doxycycline (DOX)-treated group. And then 5 mice were randomly selected for Western Blot to detect the expression of MMP9, and the other five for the immunohistochemistry to detect vWF. ICH model was induced by injection collagenase type VII into right globus pallidus stereotaxically, and DOX, a broad-spectrum MMP inhibitor, was injected by intraperitoneally at 7 days after ICH induction. Neurological severity score (NSS), corner turn test and foot-fault test were used to investigate the neurological function. And vWF-positive vessels were counted around the hematoma. Results: At 7 days, there is no difference between the two ICH-induced groups in NSS, corner turn test, foot-fault test; while at 14 days, the NSS in ICH group is significantly lower than that of DOX-treated group ( P <0.05), and the times for right-turn and foot-fault in ICH group are notably fewer than those of DOX-treated group ( P <0.05); At 14d, the number of vWF-postive microvessel in ICH group was significantly larger than that of DOX-treated group ( P <0.01), and Western Blot revealed that DOX decreased MMP9 expression remarkably( P <0.01). Conclusion: Matrix metalloproteinases were involved in the regulation of angiogenesis after ICH.