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Rodent ischemic stroke models and their relevance in preclinical research
Maria Thaysen1, Emil Westi2, Andrew N Clarkson3
1Department of Pharmacy, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark.
Abstract:
Stroke is a leading cause of death and disability worldwide, with ischemic stroke caused by an occluded vessel accounting for the majority of cases. Current treatments are limited to recanalization, either through thrombectomy or thrombolysis. Approved pharmacological interventions to suppress stroke-associated excitotoxicity and neuroinflammatory events, leading to brain tissue death, are still lacking. Although numerous preclinical studies have been performed, they have yet to be translated into clinically relevant interventions. First-line preclinical in vivo studies include the use of rodent ischemic stroke models, which vary in terms of how well they replicate human stroke pathophysiology and phenotype (including the formation of blood clot, blood-brain barrier disruption, neuroinflammation, and edema generation). Thus, rodent ischemic stroke models must be carefully chosen according to the specific pharmacological intervention to be tested. In this review, we aimed to provide an overview of the five most commonly used rodent ischemic stroke models and critically assess their advantages and limitations, with a primary focus on the acute phases of stroke.
Insights
Choosing the right rodent ischemic stroke model is crucial for developing new stroke treatments. This review assesses five common models to improve preclinical research for stroke neuroprotection.
Area of Science:
- Neuroscience
- Pharmacology
- Translational Medicine
Background:
- Stroke, particularly ischemic stroke, is a major global health challenge causing significant death and disability.
- Current treatments focus on vessel recanalization, but effective pharmacological therapies targeting excitotoxicity and neuroinflammation are still needed.
- Preclinical rodent models are essential for testing new stroke interventions, but their ability to replicate human stroke pathophysiology varies.
Purpose of the Study:
- To provide an overview of the five most frequently used rodent ischemic stroke models.
- To critically evaluate the advantages and limitations of each model.
- To guide the selection of appropriate models for testing acute-phase stroke pharmacological interventions.
Main Methods:
- Review of existing literature on commonly used rodent ischemic stroke models.
- Comparative analysis of model characteristics, including relevance to human stroke pathophysiology (e.g., clot formation, blood-brain barrier disruption, neuroinflammation, edema).
- Focus on suitability for evaluating acute stroke interventions.
Main Results:
- Detailed description of five key rodent ischemic stroke models.
- Identification of specific strengths and weaknesses of each model in replicating human stroke.
- Emphasis on how model selection impacts the translation of preclinical findings.
Conclusions:
- No single rodent model perfectly replicates human ischemic stroke.
- Careful selection of a rodent model, based on the specific pharmacological target and stroke phase, is critical for successful preclinical research.
- Improved model selection can enhance the translation of basic science discoveries into effective clinical stroke therapies.
