Skip to Main content Skip to Navigation
Journal articles

Age and albumin D site-binding protein control tissue plasminogen activator levels: neurotoxic impact.

Abstract : Recombinant tissue-type plasminogen activator (tPA) is the fibrinolytic drug of choice to treat stroke patients. However, a growing body of evidence indicates that besides its beneficial thrombolytic role, tPA can also have a deleterious effect on the ischaemic brain. Although ageing influences stroke incidence, complications and outcome, age-dependent relationships between endogenous tPA and stroke injuries have not been investigated yet. Here, we report that ageing is associated with a selective lowering of brain tPA expression in the murine brain. Moreover, our results show that albumin D site-binding protein (DBP) as a key age-associated regulator of the neuronal transcription of tPA. Additionally, inhibition of DBP-mediated tPA expression confers in vitro neuroprotection. Accordingly, reduced levels of tPA in old mice are associated with smaller excitotoxic/ischaemic injuries and protection of the permeability of the neurovascular unit during cerebral ischaemia. Likewise, we provide neuroradiological evidence indicating the existence of an inverse relationship between age and the volume of the ischaemic lesion in patients with acute ischaemic stroke. Together, these results indicate that the relationship among DBP, tPA and ageing play an important role in the outcome of cerebral ischaemia.
Document type :
Journal articles
Complete list of metadatas

Cited literature [48 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01296806
Contributor : Benoit Roussel <>
Submitted on : Friday, April 1, 2016 - 3:44:31 PM
Last modification on : Monday, November 16, 2020 - 4:26:02 PM
Long-term archiving on: : Sunday, July 3, 2016 - 12:16:06 PM

File

2009 Roussel Brain.pdf
Publisher files allowed on an open archive

Identifiers

Citation

Benoit Roussel, Richard Macrez, Amandine Jullienne, Véronique Agin, Eric Maubert, et al.. Age and albumin D site-binding protein control tissue plasminogen activator levels: neurotoxic impact.. Brain - A Journal of Neurology , Oxford University Press (OUP), 2009, 132 (Pt 8), pp.2219-30. ⟨10.1093/brain/awp162⟩. ⟨inserm-01296806⟩

Share

Metrics

Record views

677

Files downloads

980