Increases in matrix metalloproteinase-9 mRNA expression after haemorrhagic stroke

Abstract

Background: Early diagnosis and risk-stratification of stroke may lead to early therapy. A blood-based marker is required to facilitate early diagnosis and to predict outcomes. Matrix metalloproteinase-9 (MMP9) is released from degranulating neutrophils during the inflammatory response that follows stroke. MMP9 is cytotoxic and causes blood–brain barrier breakdown. We investigated MMP9 messenger RNA expression levels in leucocytes within 24 h of stroke as a diagnostic and prognostic marker. Methods: Blood was obtained within 24 h of stroke onset. Buffy coat was harvested and processed using standard techniques. Blood samples were processed from 19 controls. MMP9 mRNA concentration was measured by one-step real-time quantitative PCR assay. MMP9 concentration was expressed as copies/pg glyceraldehyde-3- phosphate dehydrogenase. Primary outcome measures were 6- month post-stroke modified Rankin score (mRS). mRS0–2 was classified as good outcome; mRS3–6 was classified as poor outcome; patients who died within 6 months were mRS6. Results: 65 adult patients (31 men) with a median age of 74 years (range 44–92) were recruited from the emergency department with informed consent and institutional ethical approval. Twenty patients were confirmed to have haemorrhagic stroke by computed tomography/magnetic resonance imaging within 24 h of admission. Eight patients died (four haemorrhages), 27 patients had a poor outcome (10 haemorrhages) and 30 patients had a good outcome (six haemorrhages). MMP9 mRNA concentrations were significantly higher in patients with haemorrhage than in patients with ischaemic stroke and controls (less than p,0.001, post-hoc test), and significantly higher in patients with adverse post-stroke Rankin scores compared with patients with good scores and controls (less than p,0.001). In patients with haemorrhage, MMP9 mRNA concentrations were significantly higher in patients with poor outcomes than in patients with good outcomes. Conclusion: Early MMP9 mRNA expression increased significantly in haemorrhagic stroke patients with poor outcomes. MMP9 mRNA expression in leucocytes may be useful for the differentiation of haemorrhagic and ischaemic causes of stroke and may predict mortality and morbidity.