Mechanism Explains Toxicity of Late tPA After Stroke

Toxicity mediated by protein activated by tissue plasminogen activator

MONDAY, June 23 (HealthDay News) -- A protein activated by tissue plasminogen activator (tPA) may explain why administering tPA more than three hours after a stroke can lead to hemorrhagic complications, according to the results of a study published online June 22 in Nature Medicine.

Having previously shown that platelet-derived growth factor-CC (PDGF-CC) is cleaved and activated by tPA, Enming J. Su, Ph.D., from the University of Michigan Medical School in Ann Arbor, and colleagues investigated whether PDGF-CC regulates blood-brain barrier integrity.

The researchers found that in the absence of ischemia, intraventricular injection of mice with tPA or active PDGF-CC significantly increased cerebrovascular permeability, which was reversed by antibodies against PDGF-CC. The increased permeability was mediated through PDGF-alpha receptors on perivascular astrocytes, and blocking the receptor with an antibody after ischemic stroke reduced both the increased permeability and hemorrhagic complications observed after late administration of tPA.

"These data demonstrate that PDGF signaling regulates blood-brain barrier permeability and suggest potential new strategies for stroke treatment," Su and colleagues conclude.

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