Matrix Metalloproteinases in Acute Intracerebral Hemorrhage

Spontaneous intracerebral hemorrhage (ICH) accounts for 10-30% of all strokes and affects more than one million people every year worldwide, and it is the stroke subtype associated with the highest rates of mortality and residual disability. So far, clinical trials have mainly targeted primary cerebral injury and have substantially failed to improve clinical outcomes. The understanding of the pathophysiology of early and delayed injury after ICH is, hence, of paramount importance to identify potential targets of intervention and develop effective therapeutic strategies. Matrix metalloproteinases (MMPs) represent a ubiquitous superfamily of structurally related zinc-dependent endopeptidases able to degrade any component of the extracellular matrix. They are upregulated after ICH, in which different cell types, including leukocytes, activated microglia, neurons, and endothelial cells, are involved in their synthesis and secretion. The aim of this review is to summarize the available experimental and clinical evidence about the role of MMPs in brain injury following spontaneous ICH and provide critical insights into the underlying mechanisms.