scholarly journals Enhanced hippocampal long-term potentiation and learning by increased neuronal expression of tissue-type plasminogen activator in transgenic mice

1999 ◽  
Vol 18 (11) ◽  
pp. 3007-3012 ◽  
Author(s):  
R. Madani
Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
pp. 2697-2704 ◽  
Author(s):  
Alexander C. Flint ◽  
Andrew L. Avins ◽  
Abigail Eaton ◽  
Stephen Uong ◽  
Sean P. Cullen ◽  
...  

Background and Purpose: In large artery occlusion stroke, both intravenous (IV) tPA (tissue-type plasminogen activator) and endovascular stroke treatment (EST) are standard-of-care. It is unknown how often tPA causes distal embolization, in which a procedurally accessible large artery occlusion is converted to a more distal and potentially inaccessible occlusion. Methods: We analyzed data from a decentralized stroke telemedicine program in an integrated healthcare delivery system covering 21 hospitals, with 2 high-volume EST centers. We captured all cases sent for EST and examined the relationship between IV tPA administration and the rate of distal embolization, the rate of target recanalization (modified Treatment in Cerebral Infarction scale 2b/3), clinical improvement before EST, and short-term and long-term clinical outcomes. Results: Distal embolization before EST was quite common (63/314 [20.1%]) and occurred more often after IV tPA before EST (57/229 [24.9%]) than among those not receiving IV tPA (6/85 [7.1%]; P <0.001). Distal embolization was associated with an inability to attempt EST: after distal embolization, 26/63 (41.3%) could not have attempted EST because of the new clot location, while in cases without distal embolization, only 8/249 (3.2%) were unable to have attempted EST ( P <0.001). Among patients who received IV tPA, 13/242 (5.4%) had sufficient symptom improvement that a catheter angiogram was not performed; 6/342 (2.5%) had improvement to within 2 points of their baseline NIHSS. At catheter angiogram, 2/229 (0.9%) of patients who had received tPA had complete recanalization without distal embolization. Both IV tPA and EST recanalization were associated with improved long-term outcome. Conclusions: IV tPA administration before EST for large artery occlusion is associated with distal embolization, which in turn may reduce the chance that EST can be attempted and recanalization achieved. At the same time, some IV tPA-treated patients show symptomatic improvement and complete recanalization. Because IV tPA is associated with both distal embolization and improved long-term clinical outcome, there is a need for prospective clinical trials testing the net benefit or harm of IV tPA before EST.


1996 ◽  
Vol 129 (1-2) ◽  
pp. 191-202 ◽  
Author(s):  
J.L.M. Heeremans ◽  
F.W. Mijnheer ◽  
H.R. Gerritsen ◽  
R. Prevost ◽  
C. Kluft ◽  
...  

1987 ◽  
Vol 26 (05) ◽  
pp. 224-228 ◽  
Author(s):  
Y. Isaka ◽  
H. Etani ◽  
K. Kimura ◽  
S. Yoneda ◽  
T. Kamada ◽  
...  

Tissue-type plasminogen activator (t-PA) which has a high affinity for fibrin in the clot, was labeled with 131I by the iodogen method, and its binding to de-endothelialized lesions in the rabbit was measured to assess the detectability of thrombi. The de-endothelialized lesion was induced in the abdominal aorta with a Fogarty 4F balloon catheter. Two hours after the de-endothelialization, 131I-labeled t-PA (125 ± 46 μCi) was injected intravenously. The initial half-life of the agent in blood (n = 12) was 2.9 ± 0.4 min. The degree of binding of 131I-labeled t-PA to the de-endothelialized lesion was evaluated at 15 min (n = 6) or at 30 min (n = 6) after injection of the agent. In spite of the retention of the biochemical properties of 131I-labeled t-PA and the presence of fibrin deposition at the de-endothelialized lesion, the binding of t-PA to the lesion was not sufficiently strong. Lesion-to-control ratios (cpm/g/cpm/g) were 1.65 ± 0.40 (at 15 min) and 1.39 ± 1.31 (at 30 min), and lesion-to-blood ratios were 1.39 ± 0.32 (at 15 min) and 1.36 ± 0.23 (at 30 min). These results suggest that radiolabeled t-PA may be inappropriate as a radiopharmaceutical for the scintigraphic detection of a pre-existing thrombotic lesion.


1988 ◽  
Vol 60 (02) ◽  
pp. 255-261 ◽  
Author(s):  
A Hotchkiss ◽  
C J Refino ◽  
C K Leonard ◽  
J V O'Connor ◽  
C Crowley ◽  
...  

SummaryModification of the carbohydrate structures of recombinant tissue-type plasminogen activator (rt-PA) can increase or decrease its rate of clearance in rabbits. When rt-PA was treated with sodium periodate to oxidize carbohydrate residues, the rate of clearance was decreased from 9.6 ± 1.9 ml min−1 kg−1 to 3.5 ± 0.6 ml min−1 kg−1 (mean ± SD, n = 5). A similar change in the clearance of rt-PA was introduced by the use of endo-β-N-acetyl- glucosaminidase H (Endo-H), which selectively removes high mannose asparagine-linked oligosaccharides; the clearance of Endo-H-treated rt-PA was 5.0 ± 0.5 ml min−1 kg−1. A mutant of rt-PA was produced with an amino acid substitution at position 117 (Asn replaced with Gin) to remove a potential glycosylation site that normally contains a high mannose structure. The clearance of this material was also decreased, similar to the periodate and Endo-H-treated rt-PA. Conversely, when rt-PA was produced in the CHO 15B cell line, which can produce only high mannose oligosaccharide structures on glycoproteins, the clearance was increased by a factor of 1.8. These results demonstrate that the removal of rt-PA from the blood depends significantly upon the nature of its oligosaccharide structures.


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