Experimental Animal Models of Ischemic Stroke

Experimental animal models of ischaemic stroke are indispensable for unravelling the complex pathophysiology of cerebral infarction and for preclinical testing of novel interventions. Rodent models dominate the field, with intraluminal filament occlusion of the middle cerebral artery, photothrombotic infarction under the skull and targeted embolic approaches each offering distinct advantages in reproducibility, lesion localisation and the possibility of reperfusion. Larger gyrencephalic species such as swine and nonhuman primates provide closer anatomical and physiological similarity to the human brain but demand more refined surgical or endovascular techniques to mimic focal arterial occlusion. Innovations in real‐time imaging, genetic manipulation and minimally invasive delivery of thrombotic agents have refined these models, enabling continuous monitoring of cerebral blood flow, microvascular thrombosis and functional outcomes. Collectively, these platforms underpin translational efforts to predict the efficacy of reperfusion therapies, neuroprotective compounds and rehabilitation strategies in human stroke.

Research from Nature Portfolio

Recent studies have introduced a novel polydopamine-hybridised iron oxide nanoparticle contrast agent that unmasks microthrombi in a mouse thromboembolic model by producing distinct hypointense signals on T2*-weighted MRI, thereby facilitating non-invasive in vivo diagnosis and monitoring of downstream microvascular occlusion. Complementing this, an artery-targeted photothrombosis approach confines photochemical damage to surface pial vessels, producing a more graded penumbra and stimulating peri-infarct neovascularisation while maintaining lesion reproducibility and modelling skilled forelimb impairments. These refinements bridge gaps between traditional photothrombotic infarcts and human stroke by better emulating the spatial heterogeneity and functional sequelae observed in patients.

Experimental Animal Models of Ischemic Stroke publication trend

The graph below shows the total number of articles in experimental animal models of ischemic stroke across all publications each year (not limited to Nature Index journals).

Technical terms

Middle cerebral artery occlusion (MCAO): A common technique to induce focal ischaemia by blocking the main cerebral artery supplying lateral brain regions, typically using an intraluminal filament or chemical agent.

Photothrombosis: A method of inducing localized cortical infarcts by photoactivation of a circulating dye to produce thrombi in targeted vessels through the intact skull.

Penumbra: The zone of tissue surrounding a core infarct that remains at risk but potentially salvageable, characterised by reduced perfusion and electrical silence.

Microthrombi: Tiny clots in the microcirculation that impede downstream capillary flow, often undetectable by conventional imaging.

Embolisation: The deliberate introduction of clotting or occlusive material into an artery to mimic embolic stroke by obstructing blood flow.

Functional ultrasound imaging (fUS): A high-resolution technique for real-time monitoring of cerebral blood volume and flow dynamics, enabling functional mapping without contrast agents or anaesthesia.

References

1. MRI-based microthrombi detection in stroke with polydopamine iron oxide. Nature Communications (2024).
2. Artery targeted photothrombosis widens the vascular penumbra, instigates peri-infarct neovascularization and models forelimb impairments. Scientific Reports (2019).
3. A Reliable Nonhuman Primate Model of Ischemic Stroke with Reproducible Infarct Size and Long-term Sensorimotor Deficits. Aging and Disease (2023).
4. Functional ultrasound imaging of stroke in awake rats. eLife (2023).
5. Establishment of a reproducible and minimally invasive ischemic stroke model in swine. JCI Insight (2023).
6. Ischemic stroke: experimental models and reality. Acta Neuropathologica (2017).