MMP-3 serum levels than patients without dCVS. Given an increased permeability of the blood-brain barrier in patients with SAH this elevation may be caused by LY294002 astrocytic MMP-3 production in our study population correlating with the time at highest risk for CVS. In contrast to the early up-regulation of MMP-9 in SAH patients compared to healthy controls, MMP-3 remained continuously lower. MMP-3 is known to activate MMP-9. Therefore, one possible explanation for the observed imbalance of MMP-3 and -9 might be a counterregulatory decrease of MMP3 in response to overactivity of MMP-9. Similar dynamics have been described in patients suffering from ischemic stroke. Notably, MMP-3 has been shown to be linked to coagulation. Therefore, the sharp decrease of MMP-3 levels during the first days after SAH might be attributable to increased consumption of coagulatory factors, triggered by aneurysm rupture. The expression of MMPs under physiologic conditions is mainly controlled at the transcriptional level. A tight balance between MMP activity and their endogenous tissue inhibitors is crucial. TIMP-1 is highly inhibitory for MMP-9. We found a delayed increase of TIMP-1 in SAH patients starting on day 6 indicating an overshoot of MMP activity during the initial phase after SAH. This is the first study that investigates TIMP-1 serum concentrations in SAH patients so far. However, animal studies suggest an upregulation of TIMP-1 after experimental SAH. In line with the delayed increase of TIMP-1, TIMP-3 was significantly reduced in the acute phase after SAH. Since TIMP-3 has been shown to have anti-inflammatory effects this downregulation might corroborate the importance of pro-inflammatory mechanisms in the pathophysiology of SAH in general and for early brain injury in particular. Our study, designed as a pilot study, only included a small number of patients, a potentially limiting factor. Importantly, the statistical models were corrected for important covariates and patients were well matched and showed a representative distribution of SJN 2511 ALK inhibitor demographic and clinical characteristics. In addition the incidence of CVS, DCI and mortality was similar to previously local and international published data. However due to the low sample size our results will have to be verified in a larger patient sample. To our knowledge this is the first longitudinal study focusing on MMPs and their respective tissue inhibitors in SAH. Early changes of MMPs and their tissue inhibitors were observed, they might play a role in the pathophysiology of acute SAH. These high-priority bioterrorism agents are defined by their ability to be easily disseminated or transmitted, their high mortality rates or capacity to generate major public health impacts, their potential for causing mass panic and social disruption, and the requirement for government action to ensure public preparedness. Moreover, there is a paucity of FDA-approved therapeutic options for the bacterial agents and no approved therapeutics for the viral pathogens. The threat of these biological agents is exacerbated by the incessant risk that these agents could become resistant to current therapeutic agents by conventional as well as genetic means. In addition, there is no effective way to address the threats of emerging, engineered, or advanced pathogens in a timely manner, as the current drug discovery and development paradigm takes up to 20 years for introduction of a new, approved drug into the market.