rt-PA causes a dose-dependent increase in the extravasation of cellular and non-cellular blood elements after focal cerebral ischemia

Brain Res. 2007 Aug 20;1164:55-62. doi: 10.1016/j.brainres.2007.05.066. Epub 2007 Jun 14.


While recombinant tissue plasminogen activator (rt-PA) is successfully used for thrombolysis in human stroke, it may increase the risk of hemorrhagic complications. We describe the effects of different doses of rt-PA (saline, 0.9, 9, or 18 mg rt-PA/kg body weight) on the extravasation of blood components following experimental cerebral ischemia (3 h, 24 h reperfusion, suture model) in rats. The damage to the blood-brain barrier and the hemoglobin extravasation were quantified by Western blotting and immunohistochemistry. Both were significantly elevated in the ischemic cortex and basal ganglia. As rt-PA doses rose, the hemoglobin content as well as the damage to the blood-brain barrier in the ischemic side also rose significantly (p<0.001). This correlated significantly with the rising MMP-9 (matrix metalloproteinase) after increasing doses of rt-PA. Despite various benefits, rt-PA is responsible for a dose-dependent increase of edema and hemorrhage after cerebral ischemia. Clinicians should consider using the lowest effective dose of rt-PA in stroke patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / physiopathology
  • Brain Edema / chemically induced*
  • Brain Edema / physiopathology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / physiopathology
  • Cerebral Arteries / drug effects
  • Cerebral Arteries / physiopathology
  • Cerebral Hemorrhage / chemically induced*
  • Cerebral Hemorrhage / physiopathology
  • Dose-Response Relationship, Drug
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use
  • Hemoglobins / drug effects
  • Hemoglobins / metabolism
  • Male
  • Matrix Metalloproteinase 9 / drug effects
  • Matrix Metalloproteinase 9 / metabolism
  • Prosencephalon / blood supply
  • Prosencephalon / drug effects
  • Prosencephalon / physiopathology
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / chemically induced*
  • Reperfusion Injury / physiopathology
  • Tissue Plasminogen Activator / adverse effects*
  • Tissue Plasminogen Activator / therapeutic use


  • Fibrinolytic Agents
  • Hemoglobins
  • Tissue Plasminogen Activator
  • Matrix Metalloproteinase 9