The main findings of this study are that: 1) MMP-9 and TIMP1 serum concentrations are significantly higher in SAH patients compared to healthy controls, 2) serum levels of MMP-9 and MMP-3 are significantly elevated in patients with dCVS compared to patients without dCVS, 3) this divergence starts in the very early phase of disease showing strongly differing values already on the second day after bleeding, and 4) both, MMP-3 and TIMP-3 are significantly decreased during the first days after spontaneous SAH. Numerous studies suggest a crucial role of MMP-9 in the pathophysiology of aneurysmal SAH. Downregulation of proinflammatory mediators – including MMP-9 – was found to AZD2281 reduce the cerebrovascular inflammatory response and late cerebral ischemia after experimental SAH. MMP-9 is responsible for inactivation of plasma-type gelsolin, an antiinflammatory mediator. Decreased levels of plasma-type gelsolin have been found in SAH patients in combination with elevated cerebrospinal fluid levels of MMP-9. These findings suggest that one way of MMP-9 action in SAH is the inactivation of a sufficient anti-inflammatory response. Treatments aiming at the inhibition of neutrophil activity, including MMP-9 release, during the early phase after SAH have reduced microvascular injury and contributed to improved outcome after experimental SAH. The pivotal role of MMP-9 during the acute phase after SAH is underlined by animal studies using the MMP-9 antagonist minocycline, which has been shown to improve outcome after SAH in rats. Changes of MMPs and TIMPs in our patients might be attributable to an increased pro-inflammatory state after acute SAH. Inflammation cascades consist of a variety of factors, MMPs and TIMPs mirroring only a minor aspect of these complex pathways. However, major parameters associated with inflammation including WBCs, CRP and body temperature, have been controlled for indicating a predominant role of MMP-9, -3, TIMP-1 and -3 in the pathophysiology after aneurysmal SAH. Mean MMP-9 as wells as the MMP-9/TIMP-1 ratio were elevated in patients with dCVS in our study population. Data regarding the association of MMP-9 with the development of cerebral vasospasm are contradictory. Chou and colleagues did not find any association between MMP-9 levels and the occurrence of cerebral vasospasm. They report an elevation of MMP-9 during the first days after SAH. This is in contrast to our findings showing an increase of MMP-9 not only during the early phase after SAH, but also during later stages, when cerebral vasospasm has been found to be present. Interestingly, elevated levels of MMP-9 were not only associated with cerebral vasospasm in our study population but also with the presence of cerebral ischemia attributable to cerebral vasospasm. Yet, this association was not transferable to 6 month outcome. This might be a consequence of the limited number of patients with cerebral ischemia since an increase of MMP-9 has been described in numerous animal and clinical stroke studies underlining the importance of MMP-9 in cerebral ischemia. MMP-9 has a pivotal function as a cleavage molecule for a variety of proteins including the activation of Endothelin-1, which has been considered an important factor in the pathophysiology of cerebral vasospasm. Interestingly, LY2157299 Endothelin-1 leads to increased production of MMP-3 in astrocytes. In the present study patients with dCVS revealed significantly.