Mouse model of in situ thromboembolic stroke and reperfusion.
OBJECTIVE
Early reperfusion using tissue-type plasminogen activator is the only therapeutic agent to treat focal cerebral ischemia with proven efficacy in patients. Nevertheless, novel insights into the pathophysiology of neurons, glial cells, and the fate of the endothelium after stroke call for the use of new strategies to improve stroke treatment alone or in combination with tissue-type plasminogen activator-induced thrombolysis. Unfortunately, despite the plethora of drugs that display clear beneficial effects in animal models of experimental ischemia, their subsequent use in clinical trials has proven disappointing. As such, one is forced to consider that new animal models of focal cerebral ischemia may be required before clinical evaluation of a new molecule.


METHODS
In situ microinjection of purified murine thrombin was used to trigger a local clot formation in anesthetized mice. Cerebral blood velocity was measured continuously throughout the duration of the study. The efficiency of recombinant tissue-type plasminogen activator to induce thrombolysis and its subsequent effect on infarct volume were then measured.


RESULTS
In situ thrombin injection leads to a reproducible clot formation and cortical brain injury. Recombinant tissue-type plasminogen activator-induced thrombolysis reduced infarct volume by 36.8% when compared with untreated control mice.


CONCLUSIONS
We describe an original and reproducible mouse model of in situ clot formation and reperfusion, which could be used to investigate new therapeutic strategies to improve stroke treatment.
Orset
Cyrille
C
INSERM-Avenir tPA in the working brain, University of Caen, Centre CYCERON, Bd Becquerel, BP 5229, 14074 Caen Cedex, France.
Macrez
Richard
R
Young
Alan R
AR
Panthou
Didier
D
Angles-Cano
Eduardo
E
Maubert
Eric
E
Agin
Veronique
V
Vivien
Denis
D
D000818:Animals; D002544:Cerebral Infarction / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D020766:Intracranial Embolism / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D009043:Motor Activity; D015424:Reperfusion; D015203:Reproducibility of Results; D013917:Thrombin; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D005343:Fibrinolytic Agents; D013917:Thrombin; D010959:Tissue Plasminogen Activator