Association of Serum Dystroglycan, MMP-2/9 and AQP-4 with Haematoma Expansion in Patients with Intracerebral Haemorrhage.

Abstract

ObjectiveThe purpose of this study was to explore association of serum dystroglycan (DG), matrix metalloproteinase-2/matrix metalloproteinase-9 (MMP-2/9), and aquaporin-4 (AQP-4) expression and haematoma expansion in patients with intracerebral haemorrhage (ICH), which are proteins involved in maintaining the integrity of the blood-brain barrier.MethodsWe included patients older than 18 years old with ICH who had undergone baseline CT within 6 hours after intracerebral haemorrhage symptom onset in our hospital between April 2018 and December 2018. Two readers independently assessed haematoma volume and other imaging information upon admission and again within 24 hours. All patients underwent 5 mL of venous blood collection 6 and 24 hours after admission. Serum expression levels of dystroglycan, matrix metalloproteinase-2/matrix metalloproteinase-9 and aquaporin-4 were determined by quantitative enzyme-linked immunosorbent assay (ELISA). Repeated analysis of variance was used to determine whether expression of the four proteins in patients with cerebral haemorrhage changed within 24 hours and whether there were differences between the haematoma enlargement and non-haematoma enlargement groups over time. Univariate and multivariate logistic regression analyses were used to compare the correlation among expression of the four proteins, clinical characteristics of patients and haematoma enlargement.ResultsExpression levels of serum matrix metalloproteinase-2/matrix metalloproteinases-9 and aquaporin-4 gradually increased within 24 hours in patients with cerebral haemorrhage (P<0.001), while expression levels of dystroglycan gradually decreased (P<0.01). Expression of serum matrix metalloproteinases-9 6 hours after onset was independently correlated with the expansion of cerebral haemorrhage. The ROC curve (AUC=0.778, 95% Cl: 0.661–0.894, P<0.001) exhibited high sensitivity (0.900) and low specificity (0.642).ConclusionThese data support that expression of MMP-9 in peripheral blood is independently correlated with the enlargement of haematoma in patients with intracerebral haemorrhage 6 hours after onset and can be used as an independent predictor of haematoma enlargement in patients with intracerebral haemorrhage. However, although the expression of MMP-2, AQP-4 and DG exhibited some changes within 6 and 24 hours after onset, they were not independently correlated with early haematoma enlargement in patients with intracerebral haemorrhage. Further multi-time point exploration and expansion of the sample size is necessary in future studies.