The mechanism that may cause the undesirable bleeding associated with blood clot 'dissolving' enzymes is described in a paper published online in Nature Medicine.
Cases of stroke caused by blood clots can be treated with tissue plasminogen activator (tPA), which 'dissolves' the clot but they can also lead to the nasty side effect of cerebral bleeding.
Daniel Lawrence and colleagues report that an intracerebral injection of tPA increases the permeability of cerebral blood vessels by activating a molecule known as platelet-derived growth factor-CC (PDGF-CC). Injection of PDGF-CC has an effect on blood vessels similar to that of tPA, whereas co-injection of antibodies against PDGF-CC blocks the increased permeability caused by tPA.
The authors also found that the effects of PDGF-CC depend on the activation of PDGF-alpha receptors present on brain cells lining the blood vessels. The treatment of mice with the PDGF-alpha receptor antagonist imatinib (Gleevec), which is clinically used to treat certain blood cancers, reduces vascular permeability and the hemorrhagic complications of tPA administration after stroke.
These results reveal a role for PDGF signaling in the regulation of the blood-brain barrier and identify imatinib as a potential drug to reduce the complications associated with the use of tPA in stroke.
Daniel Lawrence (University of Michigan Medical School, Ann Arbor, MI, USA)
Abstract available online.
(C) Nature Medicine press release.
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