A Mouse Model of Hemorrhagic Transformation by Delayed Tissue Plasminogen Activator Administration After In Situ Thromboembolic Stroke

@article{GarcaYbenes2011AMM,
  title={A Mouse Model of Hemorrhagic Transformation by Delayed Tissue Plasminogen Activator Administration After In Situ Thromboembolic Stroke},
  author={Isaac Garc{\'i}a-Y{\'e}benes and M{\'o}nica Sobrado and Juan Guillermo Zarruk and Mar Castellanos and Natalia P{\'e}rez de la Ossa and Antoni D{\'a}valos and Joaqu{\'i}n Serena and Ignacio Lizasoain and Maria A. Moro},
  journal={Stroke},
  year={2011},
  volume={42},
  pages={196-203}
}
Background and Purpose— Thrombolytic treatment with tissue plasminogen activator (tPA) improves outcome of patients with stroke who can be treated within 3 hours of symptom onset. However, delayed treatment with tPA leads to increased risk of hemorrhagic transformation and can result in enhanced brain injury. The purpose of this study is to validate a reproducible mouse model of hemorrhagic transformation associated with delayed administration of tPA. Methods— Mice were anesthetized and… 

Figures and Tables from this paper

A Canine Model of Hemorrhagic Transformation Using Recombinant Tissue Plasminogen Activator Administration After Acute Ischemic Stroke
TLDR
A canine HT model is established that closely mimics human HT by using rtPA administration after the induction of middle cerebral artery occlusion (MCAO) with autologous clots and a potential mechanism underlying rtpa-caused HT may be related to BBB dysfunction induced by an increase in MMP-9 expression.
Fingolimod Reduces Hemorrhagic Transformation Associated With Delayed Tissue Plasminogen Activator Treatment in a Mouse Thromboembolic Model
TLDR
This study confirms the protective efficacy of fingolimod as a treatment against ischemic stroke in another rodent model of stroke (thromboembolic occlusion), and suggests that fingolIMod could potentially be used in combination with tPA to reduce the risk of brain hemorrhage.
Plasma kallikrein mediates brain hemorrhage and edema caused by tissue plasminogen activator therapy in mice after stroke.
TLDR
It is demonstrated that tPA activates PPK in plasma and PKal inhibition reduces cerebral complications associated with tPA-mediated thrombolysis in stroke.
Angioedema and Hemorrhage After 4.5-Hour tPA (Tissue-Type Plasminogen Activator) Thrombolysis Ameliorated by T541 via Restoring Brain Microvascular Integrity
TLDR
T541 is suggested as a potential remedy to attenuate delayed tPA-related angioedema and hemorrhage and extend time window for tPA treatment.
Extension of Tissue Plasminogen Activator Treatment Window by Granulocyte-Colony Stimulating Factor in a Thromboembolic Rat Model of Stroke
TLDR
The efficacy of G-CSF is corroborated in enhancing the therapeutic time window of tPA for stroke treatment via EPC mobilization and enhancement of vasculogenesis.
Hemorrhagic Transformation After Tissue Plasminogen Activator Treatment in Acute Ischemic Stroke.
TLDR
New potential mechanisms and possible experimental models of HT development are discussed, as well as possible biomarkers and treatment methods, and recent progress in neuroprotective strategies to improve HT after stroke treated with rt-PA is outlined.
Experimental modeling of recombinant tissue plasminogen activator effects after ischemic stroke
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 45 REFERENCES
Hemorrhagic Transformation After Fibrinolysis With Tissue Plasminogen Activator: Evaluation of Role of Hypertension With Rat Thromboembolic Stroke Model
TLDR
In this rat thromboembolic model of stroke, tPA-induced hemorrhage is dependent on blood pressure and that pharmacological reduction of hypertension during fibrinolysis can reduce the risk of hemorrhagic transformation.
Mouse Model of In Situ Thromboembolic Stroke and Reperfusion
TLDR
An original and reproducible mouse model of in situ clot formation and reperfusion is described, which could be used to investigate new therapeutic strategies to improve stroke treatment.
Reduction of Tissue Plasminogen Activator-Induced Hemorrhage and Brain Injury by Free Radical Spin Trapping after Embolic Focal Cerebral Ischemia in Rats
  • M. Asahi, K. Asahi, X. Wang, E. Lo
  • Medicine, Biology
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2000
TLDR
Combined therapies with anti-free radical treatments may reduce the severity of tPA-induced hemorrhage and brain injury after cerebral ischemia, and tPA interacts negatively with reperfusion injury to promote hemorrhage.
Involvement of Thrombolysis in Recombinant Tissue Plasminogen Activator-Induced Cerebral Hemorrhages and Effect on Infarct Volume and Postischemic Endothelial Function
TLDR
Treatment with rtPA led to intracerebral hemorrhages, in contrast to saline-treated animals, and the presence of TLP increased the severity of these hemorrhage severity, in parallel with increased infarct volume and worsened endothelial function.
Prediction of impending hemorrhagic transformation in ischemic stroke using magnetic resonance imaging in rats.
TLDR
It is suggested that acute Gd-DTPA enhancement may provide an early prediction of petechial hemorrhage, suggesting that early endothelial ischemic damage occurs before gross brain infarction and hemorrhage.
Differences in Clot Preparation Determine Outcome of Recombinant Tissue Plasminogen Activator Treatment in Experimental Thromboembolic Stroke
Background and Purpose— Thrombin-induced clots used in experimental thromboembolic stroke differ from clots forming spontaneously under clinical conditions. We investigated whether this difference
Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke
TLDR
It is indicated that site of occlusion, time to recanalization, and time to treatment are important variables in acute stroke intervention with this agent.
Safety and Efficacy of Intravenous Tissue Plasminogen Activator and Heparin in Acute Middle Cerebral Artery Stroke
TLDR
Reperfusion and effective collateral blood flow seem to be two important factors associated with a small infarct volume and good clinical outcome in patients presenting with acute ischemic stroke.
...
1
2
3
4
5
...