Matrix metalloproteinase-9 concentration in the cerebral extracellular fluid of patients during the acute phase of aneurysmal subarachnoid hemorrhage

Objectives: The pathogenesis of delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) is multi-factorial and not completely elucidated. Matrix metalloproteinase-9 (MMP-9) might participate in wall remodeling leading to luminal narrowing. The authors investigated MMP-9 concentration in brain extracellular fluid of aSAH patients and assessed whether this enzyme could have a predictive value for the risk of DCI. Methods: Patients were classified according to the grading of the World Federation of Neurological Surgeons (WFNS) in low- and high-grade patients (WFNS = 1-3, n = 9 and WFNS = 4-5, n = 12, respectively). Cerebral microdialysis probes were placed in brain parenchyma of the respective vascular territory of the aneurysm in 21 consecutive aSAH patients, enrolled in a prospective study on inflammation. Microdialysis samples, collected daily from day 0 until day 8 after aSAH, were retrospectively analyzed for MMP-9 by zymography. Results: Initial concentration of the MMP-9 proform (pro-MMP-9) was significantly higher in high-grade patients as compared to low-grade patients. Furthermore, initial pro-MMP-9 concentration in patients with DCI was seven-fold higher than in asymptomatic patients. Pro-MMP-9 values greater than or equal to 0.27 pg/mu l showed 83% sensitivity and 63% specificity in predicting vasospasm. The mature form of the MMP-9 could be preferentially detected in patients with DCI but was usually low. Discussion: The pro and mature forms of MMP-9 were released locally in the brain after aSAH. Pro-MMP-9 release was related to WFNS grade severity. This protease, considered as playing a critical role in endothelial basal membrane damage, may contribute to the inflammatory processes leading to arterial narrowing.