Metalloproteinase and stroke infarct size: role for anti-inflammatory treatment?
Deregulation of matrix metalloproteinases (MMPs), the largest class of human proteases, has been implicated in brain damage in both animal and human studies. Some MMPs are elevated after stroke (both in plasma and in brain tissue), and their expression is enhanced by t-PA during thrombolysis related to hemorrhagic transformation events. Although the exact cellular source of MMPs remains unknown, brain endothelium, astrocytes, neurons, and inflammatory-activated cells, such as neutrophils, may release MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, and/or MMP-13. Neurovascular perturbations occurring after stroke lead to blood-brain barrier leakage, edema, hemorrhage, leukocyte infiltration, and progressive inflammatory reactions to brain injury over hours or even days after the initial stroke. Synthesized MMP inhibitors and several compounds used for stroke secondary prevention, such as anti-inflammatory drugs, might decrease MMPs and improve the acute treatment of human brain ischemia without compromising the beneficial effects of matrix plasticity during stroke recovery.
Morancho
Anna
A
Neurovascular Research Laboratory, Neurology Department, Hospital Universitari Vall d'Hebron, Institut de Recerca, Universitat Autònoma de Barcelona, Spain.
Rosell
Anna
A
García-Bonilla
Lidia
L
Montaner
Joan
J
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001921:Brain / Q000201:enzymology / Q000473:pathology; D002545:Brain Ischemia / Q000201:enzymology / Q000473:pathology; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D011480:Protease Inhibitors / Q000627:therapeutic use; D020521:Stroke / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D015912:Thrombolytic Therapy
D000893:Anti-Inflammatory Agents; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D020782:Matrix Metalloproteinases