Animal models of ischemic stroke and their application in clinical research

Abstract

This review outlines the most frequently used rodent stroke models and discusses their strengths and shortcomings. Mimicking all aspects of human stroke in one animal model is not feasible because ischemic stroke in humans is a heterogeneous disorder with a complex pathophysiology. The transient or permanent middle cerebral artery occlusion (MCAo) model is one of the models that most closely simulate human ischemic stroke. Furthermore, this model is characterized by reliable and well-reproducible infarcts. Therefore, the MCAo model has been involved in the majority of studies that address pathophysiological processes or neuroprotective agents. Another model uses thromboembolic clots and thus is more convenient for investigating thrombolytic agents and pathophysiological processes after thrombolysis. However, for many reasons, preclinical stroke research has a low translational success rate. One factor might be the choice of stroke model. Whereas the therapeutic responsiveness of permanent focal stroke in humans declines significantly within 3 hours after stroke onset, the therapeutic window in animal models with prompt reperfusion is up to 12 hours, resulting in a much longer action time of the investigated agent. Another major problem of animal stroke models is that studies are mostly conducted in young animals without any comorbidity. These models differ from human stroke, which particularly affects elderly people who have various cerebrovascular risk factors. Choosing the most appropriate stroke model and optimizing the study design of preclinical trials might increase the translational potential of animal stroke models.

Protective Effect of Stachydrine Against Cerebral Ischemia-Reperfusion Injury by Reducing Inflammation and Apoptosis Through P65 and JAK2/STAT3 Signaling Pathway

“…It is well known that necrosis or apoptosis can aggravate ischemic damage. Ischemia-reperfusion injury is associated with inflammatory response and apoptosis, but the exact mechanism is unclear (Mestriner et al, 2013;Fluri et al, 2015;Hu et al, 2015). In the current study, the treatment of stachydrine significantly reduced the number of Tunel-positive cells after ischemia.…”

Ischemic stroke: experimental models and reality

“…Application onto an exposed vessel or directly on the brain surface or stereotactically injected into the brain parenchyma leads to vasoconstriction inducing downstream ischemia [37]. Using this method, more or less any region in the brain is targetable.…”

Differential distribution and functional impact of BK channel beta1 subunits across mesenteric, coronary, and different cerebral arteries of the rat

“…4, 5 and 6) and BK β1 mRNA levels (Fig. 7) when compared to those of BA or CA, 2) rat MCA is a widely used experimental model to address human cerebrovascular pathophysiology and pharmacology [3,26,33,88], and 3) we conducted all our previous studies with smooth muscle BK β1-targeting vasodilators (LCA itself, other cholanes, LTB4 and HENA) using rat MCA [15–17,19,63,74]. BK β1 protein overexpression was confirmed by Western blotting (Fig.…”