Editorial - Journal of Experimental Stroke & Translational Medicine (2025) Volume 17, Issue 2
Ischemia-Reperfusion Models: Experimental Approaches and Clinical Relevance
Michael Andersen*
Department of Physiology, University of Copenhagen, Denmark
- *Corresponding Author:
- Michael Andersen
Department of Physiology, University of Copenhagen, Denmark
E-mail: michael.andersen@ku.dk
Received: 01-March-2025, Manuscript No. jestm-25-170381; Editor assigned: 3-March-2025, PreQC No. jestm-25-170381 (PQ); Reviewed: 17-March-2025, QC No. jestm-25-170381; Revised: 24-March-2025, Manuscript No. jestm-25-170381 (R); Published: 31-March-2025, DOI: 10.37532/jestm.2024.16(6).317-318
Introduction
Ischemia-reperfusion (I/R) injury represents a paradox in clinical medicine: while restoring blood supply to ischemic tissue is essential for survival, the reperfusion process itself can aggravate tissue injury. This dual effect is especially relevant in conditions such as stroke, myocardial infarction, organ transplantation, and trauma [1]. To better understand the underlying mechanisms and test therapeutic strategies, researchers have developed a variety of ischemia-reperfusion models. These models, both in vitro and in vivo, allow controlled investigation of the pathophysiological processes involved, including oxidative stress, mitochondrial dysfunction, excitotoxicity, and inflammation.
Experimental Models of Ischemia-Reperfusion
In Vitro Models
In vitro models provide a simplified system to study cellular and molecular mechanisms of I/R injury:
Oxygen-Glucose Deprivation (OGD): Cultured neurons, astrocytes, or brain slices are deprived of oxygen and glucose, mimicking ischemia. Reoxygenation simulates reperfusion, allowing precise control of duration and severity.
Cell Line Models: Immortalized neuronal or cardiac cell lines exposed to hypoxia and reoxygenation enable mechanistic studies and drug screening [2].
These approaches offer reproducibility and mechanistic insights, but they lack the complexity of whole-organ systems.
In Vivo Cerebral I/R Models
Animal models are essential for studying systemic responses and testing therapeutic strategies:
Middle Cerebral Artery Occlusion (MCAO): The most widely used model for stroke research. A filament is inserted into the internal carotid artery to occlude the middle cerebral artery temporarily. Reperfusion occurs upon filament withdrawal. This model replicates focal ischemia seen in human stroke.
Four-Vessel Occlusion (4-VO): Produces global cerebral ischemia by occluding vertebral and carotid arteries. Often used to study hippocampal vulnerability.
Two-Vessel Occlusion (2-VO): Involves bilateral occlusion of the carotid arteries, producing chronic hypoperfusion and white matter injury.
These models closely resemble human cerebral ischemia but require surgical expertise and may have variability in outcomes.
In Vivo Myocardial I/R Models
Coronary Artery Ligation: Temporary ligation of the left anterior descending coronary artery in rodents or larger animals is the gold standard for studying myocardial infarction. Reperfusion occurs after releasing the ligature.
Isolated Heart (Langendorff Model): The heart is perfused ex vivo, enabling precise control over ischemic and reperfusion conditions while preserving cardiac function [3].
Organ Transplantation Models
I/R injury is a critical challenge in organ transplantation. Animal models involving kidney, liver, or lung ischemia followed by transplantation help assess donor organ preservation and post-transplant recovery strategies.
Mechanistic Insights from I/R Models
Studies using these models have elucidated several key mechanisms:
Oxidative Stress: Rapid reoxygenation produces reactive oxygen species, damaging DNA, proteins, and lipids.
Mitochondrial Dysfunction: Reperfusion triggers mitochondrial permeability transition, leading to cell death.
Inflammation: Infiltration of neutrophils and release of cytokines amplify tissue damage.
Endothelial Dysfunction: Increased vascular permeability contributes to edema and hemorrhage.
Apoptosis and Necrosis: Both forms of cell death are prominent following I/R.
Clinical Relevance
Insights from ischemia-reperfusion models have guided therapeutic developments:
Stroke Therapy: Preclinical findings from MCAO models paved the way for reperfusion therapies such as thrombolysis and mechanical thrombectomy [4].
Cardiac Interventions: Myocardial I/R models have informed cardioprotective strategies during angioplasty and bypass surgery.
Organ Transplantation: Experimental models have improved preservation techniques, including hypothermic and normothermic perfusion.
Despite these advances, translation from bench to bedside remains challenging. Many neuroprotective and cardioprotective drugs successful in animal models have failed in clinical trials [5], underscoring the complexity of human disease.
Conclusion
Ischemia-reperfusion models remain indispensable tools in biomedical research, offering valuable insights into the mechanisms of tissue injury and guiding the development of therapeutic interventions. From in vitro oxygen-glucose deprivation systems to in vivo models of stroke, myocardial infarction, and organ transplantation, these experimental approaches replicate key aspects of human pathology. While translation into clinical practice has been limited, ongoing refinements in model design and integrative approaches combining cellular, molecular, and systemic perspectives hold promise for bridging the gap. Ultimately, ischemia-reperfusion models continue to play a central role in advancing strategies to reduce morbidity and mortality associated with ischemic diseases.
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