Matrix Metalloproteinase 9 as a Potential Target for the Treatment of Stroke

Aneurysmal subarachnoid hemorrhage (SAH) affects 30,000 people annually. One of the most common and potentially treatable sources of neurological injury in SAH patients is delayed cerebral ischemia (DCI). Several processes underlie DCI, one of which is the severe narrowing of the intracranial arteries, a condition known as arterial vasospasm. Recent studies have linked matrix metalloproteinase 9 (MMP-9) activity with the pathophysiology of brain injury following aneurysmal SAH. Other studies have linked serum and cerebrospinal fluid (CSF) MMP-9 levels with the development of vasospasm and worsening neurological outcomes. As preliminary data for a single-institution, open label, randomized controlled Phase I trial, we looked to optimize the logistics required in serially measuring serum and CSF levels of MMP-9 expression and activity. To do so, daily CSF and serum samples were taken from 20 SAH patients and nine controls. Samples were analyzed via enzyme-linked immunosorbent assay (ELISA) to determine expression. Preliminary results suggest that MMP-9 levels continue to rise in patients with vasospasm versus those without. In addition, in patients who received an endovascular coiling, those with vasospasm were observed to have a significant elevation in serum MMP-9 expression, both in the serum profile and in mean serum expression. MMP-9 serum expression was also found to rise significantly in the second half of our study window as compared to the first half, which correlated with DCI and the onset of vasospasm. These results show that MMP-9 serum and CSF levels can effectively be measured with ELISA, and provide further evidence that MMP-9 may represent both a biomarker to monitor for vasospasm, as well as a potential therapeutic target for pharmacological agents in the treatment of DCI