Role of tissue-plasminogen activator (t-PA) in a mouse model of neonatal white matter lesions: Interaction with plasmin inhibitors and anti-inflammatory drugs

Neuroscience ◽  
2007 ◽  
Vol 146 (2) ◽  
pp. 670-678 ◽  
Author(s):  
P. Leroux ◽  
O. Hennebert ◽  
H. Legros ◽  
V. Laudenbach ◽  
P. Carmeliet ◽  
...  
Keyword(s):  
White Matter ◽  
Mouse Model ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
White Matter Lesions ◽  
Tissue Plasminogen ◽  
Inflammatory Drugs ◽  
Plasmin Inhibitors ◽  
Anti Inflammatory

scholarly journals Role of Tissue-Derived Plasminogen Activator (t-PA) in an Excitotoxic Mouse Model of Neonatal White Matter Lesions

2004 ◽  
Vol 63 (1) ◽  
pp. 53-63 ◽  
Author(s):  
Olivier Hennebert ◽  
Stéphane Marret ◽  
Peter Carmeliet ◽  
Pierre Gressens ◽  
Annie Laquerrière ◽  
...  
Keyword(s):  
White Matter ◽  
Mouse Model ◽  
Plasminogen Activator ◽  
White Matter Lesions

scholarly journals Tissue plasminogen activator prevents white matter damage following stroke

2011 ◽  
Vol 208 (6) ◽  
pp. 1229-1242 ◽  
Author(s):  
Fernando Correa ◽  
Maxime Gauberti ◽  
Jérôme Parcq ◽  
Richard Macrez ◽  
Yannick Hommet ◽  
...  
Keyword(s):  
White Matter ◽  
Plasminogen Activator ◽  
Cell Fate ◽  
Tissue Plasminogen Activator ◽  
Mechanism Of Action ◽  
White Matter Lesions ◽  
Brain Diseases ◽  
Stroke Treatment ◽  
Tissue Plasminogen ◽  
The Impact

Tissue plasminogen activator (tPA) is the only available treatment for acute stroke. In addition to its vascular fibrinolytic action, tPA exerts various effects within the brain, ranging from synaptic plasticity to control of cell fate. To date, the influence of tPA in the ischemic brain has only been investigated on neuronal, microglial, and endothelial fate. We addressed the mechanism of action of tPA on oligodendrocyte (OL) survival and on the extent of white matter lesions in stroke. We also investigated the impact of aging on these processes. We observed that, in parallel to reduced levels of tPA in OLs, white matter gets more susceptible to ischemia in old mice. Interestingly, tPA protects murine and human OLs from apoptosis through an unexpected cytokine-like effect by the virtue of its epidermal growth factor–like domain. When injected into aged animals, tPA, although toxic to the gray matter, rescues white matter from ischemia independently of its proteolytic activity. These studies reveal a novel mechanism of action of tPA and unveil OL as a target cell for cytokine effects of tPA in brain diseases. They show overall that tPA protects white matter from stroke-induced lesions, an effect which may contribute to the global benefit of tPA-based stroke treatment.

Tissue plasminogen activator (tPA) of paternal origin is necessary for the success of in vitro but not of in vivo fertilisation in the mouse

2019 ◽  
Vol 31 (3) ◽  
pp. 433 ◽  
Author(s):  
Francisco A. García-Vázquez ◽  
C. Soriano-Úbeda ◽  
R. Laguna-Barraza ◽  
M José Izquierdo-Rico ◽  
Felipe A. Navarrete ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Cumulus Cells ◽  
Human Reproduction ◽  
Sperm Binding ◽  
Tissue Plasminogen ◽  
Plasmin Inhibitors

Besides its fibrinolytic function, the plasminogen–plasmin (PLG–PLA) system is also involved in fertilisation, where plasminogen activators bind to plasminogen to produce plasmin, which modulates sperm binding to the zona pellucida. However, controversy exists, depending on the species, concerning the role of the different components of the system. This study focused its attention on the role of the PLG–PLA system on fertilisation in the mouse with special attention to tissue plasminogen activator (tPA). The presence of exogenous plasminogen reduced invitro fertilisation (IVF) rates and this decline was attenuated by the presence of plasmin inhibitors in combination with plasminogen. The incubation of spermatozoa with either oocytes or cumulus cells together with plasminogen did not change the acrosome reaction but reduced the number of spermatozoa attached. When spermatozoa from tPA−/− mice were used, the IVF rate decreased drastically, although the addition of exogenous tPA during gamete co-incubation under invitro conditions increased fertilisation success. Moreover, fertility could not be restored after invivo insemination of tPA−/− spermatozoa in the female ampulla, although tPA−/− males were able to fertilise invivo. This study suggests a regulatory role of the PLG–PLA system during fertilisation in the mouse with possible implications in human reproduction clinics, such as failures in tPA production, which could be partially resolved by the addition of exogenous tPA during IVF treatment.

Abstract WP105: Tissue Plasminogen Activator (tPA) is Essential for Functional Recovery After Stroke by Promoting Axonal Outgrowth

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Shubei Ma
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Functional Recovery ◽  
Stroke Recovery ◽  
White Matter Integrity ◽  
Blue Staining ◽  
Tissue Plasminogen

Objectives: Stroke is the leading cause of long term neurological disability with limited therapeutic options. Human recombinant tissue plasminogen activator (tPA) is currently the only FDA approved drug for the thrombolytic treatment of ischemic stroke. Emerging evidence suggests that the effects of tPA in ischemic brain may extend beyond its thrombolytic activity. In this study, we investigated the role of tPA in long term stroke recovery. Methods: Cortical infarct was induced by distal middle cerebral artery occlusion (dMCAO) in tPA knockout (KO) and wild type (WT) mice. Sensorimotor functions were evaluated at 3-35 days after dMCAO. White matter integrity was assessed by luxol fast blue staining, immunohistochemistry for SMI-32, and diffusion tensor imaging (DTI). The neuronal tracer biotinylated dextran amine (BDA) was used to label the corticorubral tract and the corticospinal tract. For rescue experiment, tPA (2mg/kg) was delivered intranasally to tPA KO mice once a day for 14 days starting 6h after dMCAO. Results: Infarct volume was comparable between tPA KO and WT mice after dMCAO. Sensorimotor deficits after dMCAO were exacerbated in tPA KO mice than WT mice. tPA KO mice also showed more severe demyelination in post-stroke white matter and reduced axonal sprouting at 35 days after dMCAO compared to WT mice. DTI studies revealed deteriorated white matter integrity in tPA KO mice, as manifested by decreased fractional anisotropy. Intranasal delivery of tPA after dMCAO rescued the neurological phenotype shown by tPA KO mice. Conclusion: Endogenous tPA promotes white matter integrity and is essential for functional recovery after ischemic stroke. tPA may be a novel neurorestorative therapy for stroke recovery.

scholarly journals Role of residue Y99 in tissue plasminogen activator

2008 ◽  
Vol 9 (3) ◽  
pp. 619-622 ◽  
Author(s):  
Alessandro Vindigni ◽  
Mollie Winfield ◽  
Youhna M. Ayala ◽  
Enrico Di Cera
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Tissue Plasminogen

In vivo clearance of tissue plasminogen activator: The complex role of sites of glycosylation and level of sialylation

1993 ◽  
Vol 7 (1) ◽  
pp. 15-22 ◽  
Author(s):  
E.S. Cole ◽  
E.H. Nichols ◽  
L. Poisson ◽  
M.L. Harnois ◽  
D.J. Livingston
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Tissue Plasminogen
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