Different strokes for different folks: the rich diversity of animal models of focal cerebral ischemia

Abstract

No single animal model is able to encompass all of the variables known to affect human ischemic stroke. This review highlights the major strengths and weaknesses of the most commonly used animal models of acute ischemic stroke in the context of matching model and experimental aim. Particular emphasis is placed on the relationships between outcome and underlying vascular variability, physiologic control, and use of models of comorbidity. The aim is to provide, for novice and expert alike, an overview of the key controllable determinants of experimental stroke outcome to help ensure the most effective application of animal models to translational research.

Figure 1

Brain size and gyral complexity.

Figure 2

Proportion of stroke models used in 2,852 neuroprotection experiments.

Figure 3

Not all rats were created equal: infarct volume variability after thread occlusion in Sprague–Dawley (SD), Wistar Kyoto (WKY), and spontaneously hypertensive rat (SHR) under a range of experimental circumstances. Blue bars represent the proportion of animals with cortical infarction. Mean and s.d. plus individual data points.

Figure 4

Circle of Willis and posterior communicating arteries of the spontaneously hypertensive rat (Ogata et al, 1976).

Figure 5

Guidelines for stroke modeling. (A) A guide to matching model characteristics to experimental aim; (B) a guide to preclinical stroke modeling required to move from a hypothesis to a clinical trial.

Figure 5

Guidelines for stroke modeling. (A) A guide to matching model characteristics to experimental aim; (B) a guide to preclinical stroke modeling required to move from a hypothesis to a clinical trial.