Tissue-type plasminogen activator crosses the intact blood-brain barrier by low-density lipoprotein receptor-related protein-mediated transcytosis.
Circulation
; 111(17): 2241-9, 2005 May 03.
Article
in En
| MEDLINE
| ID: mdl-15851587
ABSTRACT
BACKGROUND:
Accumulating evidence demonstrates a critical involvement of tissue-type plasminogen activator (tPA) in pathological and physiological brain conditions. Determining whether and how vascular tPA can cross the blood-brain barrier (BBB) to enter the brain is thus important, not only during stroke but also in physiological conditions. METHODS ANDRESULTS:
In the present work, we provide evidence in vivo that intravenous injection of tPA increases NMDA-induced striatal lesion in the absence of BBB leakage. Accordingly, we show that tPA crosses the BBB both after excitotoxic lesion and in control conditions. Indeed, vascular injected tPA can be detected within the brain parenchyma and in the cerebrospinal fluid. By using an in vitro model of BBB, we have confirmed that tPA can cross the intact BBB. Its passage was blocked at 4 degrees C, was saturable, and was independent of its proteolytic activity. We have shown that tPA crosses the BBB by transcytosis, mediated by a member of the LDL receptor-related protein family.CONCLUSIONS:
We demonstrate that blood-derived tPA can reach the brain parenchyma without alteration of the BBB. The molecular mechanism of the passage of tPA from blood to brain described here could represent an interesting target to improve thrombolysis in stroke.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Blood-Brain Barrier
/
Tissue Plasminogen Activator
/
Low Density Lipoprotein Receptor-Related Protein-1
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
Circulation
Year:
2005
Document type:
Article
Affiliation country:
France