Fibrin-modifying serine proteases thrombin, tPA, and plasmin in ischemic stroke: a review.
Ischemic stroke is a sudden loss of circulation to a portion of the brain that results in a loss of neurologic function. Many ischemic strokes are embolic. They result from a thrombus traveling into the central circulation and occluding a blood vessel. Treatment of ischemic stroke with recombinant tissue plasminogen activator (tPA) can improve patient outcomes. However, tPA must be used during a specific time window after the stroke onset to be effective and it risks converting an ischemic stroke into a hemorrhagic one. We explore the basic effects of fibrin-modifying proteases on neurons, astrocytes, and microglia during ischemia. tPA, thrombin, and plasmin can initiate microglial activation and change both neuronal and astrocytic survival. As a result of these functions and of their role in blood homeostasis, all three of these proteases have profound effects on neurons and glial cells in the brain and are capable of altering the development and severity of ischemic stroke.
Sheehan
John J
JJ
Program in Molecular and Cellular Pharmacology and Department of Pharmacological Sciences, University Medical Center at Stony Brook, Stony Brook, New York.
Tsirka
Stella E
SE
Program in Molecular and Cellular Pharmacology and Department of Pharmacological Sciences, University Medical Center at Stony Brook, Stony Brook, New York.
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism*; D005341:Fibrinolysin / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism*; D013917:Thrombin / Q000096:biosynthesis / Q000502:physiology*; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis / Q000502:physiology* / Q000627:therapeutic use
D005337:Fibrin; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin