Contribution of extracellular proteolysis and microglia to intracerebral hemorrhage.
Proteases, such as tissue plasminogen activator, thrombin, metalloproteinases, and cathepsins, have complex functions in the mammalian brain under both normal and pathological conditions. Some of these proteases are expressed by neuronal cells, whereas others are made by the immunocompetent, macrophage-like cells of the brain: the microglia. This article reviews the physiological and pathological functions of these proteinases in the brain as well as recent findings linking extracellular proteases with neuronal cell death in ischemic or hemorrhagic stroke. Better understanding of protease expression and signaling, microglial activation, and their relationship with neuronal cell death during stroke injury could contribute to the development of relevant inhibitors as novel neuroprotective agents for treating ischemic stroke and intracerebral hemorrhage.
Wang
Jian
J
Department of Pharmacological Sciences, University Medical Center at Stony Brook, Stony Brook, NY 11794-8451, USA.
Tsirka
Stella E
SE
D000818:Animals; D002403:Cathepsins / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D017628:Microglia / Q000502:physiology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D002403:Cathepsins; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator; D020782:Matrix Metalloproteinases