Extracellular proteolytic pathophysiology in the neurovascular unit after stroke.
The NINDS Stroke Progress Review Group recommended a shift in emphasis from a purely neurocentric view of cell death towards a more integrative approach whereby responses in all brain cells and matrix are considered. The neurovascular unit (fundamentally comprising endothelium, astrocyte, and neuron) provides a conceptual framework where cell-cell and cell-matrix signaling underlies the overall tissue response to stroke and its treatments. Here, we briefly review recent data on extracellular proteolytic dysfunction in the neurovascular unit after a stroke. The breakdown of neurovascular matrix initiates blood-brain barrier disruption with edema and/or hemorrhage. Endothelial dysfunction amplifies inflammatory responses. Perturbation of cell-matrix homeostasis triggers multiple cell death pathways. Interactions between the major classes of extracellular proteases from the plasminogen and matrix metalloprotease families may underlie processes responsible for some of the hemorrhagic complications of thrombolytic stroke therapy. Targeting the proteolytic imbalance within the neurovascular unit may provide new approaches for improving the safety and efficacy of thrombolytic reperfusion therapy for stroke.
Lee
Sun-Ryung
SR
Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, MA 02129, USA.
Wang
Xiaoying
X
Tsuji
Kiyoshi
K
Lo
Eng H
EH
D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D005110:Extracellular Space / Q000201:enzymology*; D006801:Humans; D007249:Inflammation; D008666:Metalloendopeptidases / Q000502:physiology; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D010447:Peptide Hydrolases / Q000502:physiology*; D020521:Stroke / Q000503:physiopathology*; D010959:Tissue Plasminogen Activator / Q000502:physiology
D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator; D008666:Metalloendopeptidases