[Experimental microvascular and clotting changes--significance for acute stroke therapy].
Ischemia and reperfusion cause significant alterations in the structure and functional integrity of the cerebral microvasculature. Clinical sequelae include cerebral oedema, haemorrhagic transformation with the extravasation of cellular blood elements, and possible parenchymal haemorrhage. Vascular changes originate from structural changes of the vascular wall and from interactions with blood components such as leukocytes. This leads to the activation of various pathophysiological cascades including the clotting system, its inhibitors,matrix metalloproteases, and serine proteases. This article focuses on the degradation of the microvascular basal lamina, which is formed by extracellular matrix proteins such as type IV collagen, fibronectin, and laminin. Extracellular matrix proteins are degraded by matrix metalloproteases and serine proteases. Tissue plasminogen activator (t-PA), a serine protease commonly administered for thrombolysis, activates matrix metalloproteinases in turn, amplifying local proteolytic activity. Clinical implications and possible therapeutic strategies are discussed.
Wagner
S
S
Neurologische Klinik, Ruprecht-Karls-Universität Heidelberg.
Hamann
G F
GF
D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000503:physiopathology; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000098:blood supply*; D002544:Cerebral Infarction / Q000188:drug therapy / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D020766:Intracranial Embolism / Q000188:drug therapy / Q000503:physiopathology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D015427:Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology*; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use
D016326:Extracellular Matrix Proteins; D010959:Tissue Plasminogen Activator; D020782:Matrix Metalloproteinases