To mimic ischemic stroke in mice, thrombin is directly injected in the middle cerebral artery to prompt clot formation. This reproducible stroke model can be used to investigate fibrinolytic interventions and novel strategies to improve stroke therapy or prevention.
All therapeutic strategies validated in animal stroke models have failed in clinical settings, except tissue-type plasminogen activator (tPA)-induced thrombolysis. To better mimic the human stroke pathology and to test new therapeutic strategies, we describe here a mouse stroke model based on in situ clot formation.
The injection of thrombin in the middle cerebral artery results in the conversion of fibrinogen into fibrin, leading to clot formation and subsequent reproducible ischemic brain damages. In this model, tPA administration during the therapeutic window is beneficial, whereas late administration is deleterious.
The craniotomy performed during the surgery may reduce the additional deleterious consequences of raised intracranial pressure normally associated with cerebral ischemia and thus limit the final infarct volume due to the occlusion. This model of in situ clot formation and reperfusion is a relevant translational stroke model, close to the human stroke pathology. It should be an appropriate model to test new thrombolytics and/or neuroprotective strategies prior to clinical trials.
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This work was supported by the “Institut National de la Santé Et de la Recherche Médicale” (INSERM), the French Ministry of Research and Technology, and the Eurostroke-Arise Program (FP7/2007-2013-201024).
All authors report no disclosure.
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