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Ischemic Stroke, Lessons from the Past towards Effective Preclinical Models.
Beatriz Amado1,2, Lúcia Melo1,2, Raquel Pinto1,2
1Molecular Neurobiology Group, IBMC-Instituto de Biologia Molecular e Celular, 4200-135 Porto, Portugal.
Biomedicines
|October 27, 2022
Summary
Advancements in stroke models, including organoids and improved mouse models, enhance the evaluation of new brain-protective therapies. These models better predict clinical outcomes, improving stroke treatment and reducing patient disability.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Pharmacology
Background:
- Ischemic stroke remains a major global health concern, with current treatments focused on reperfusion.
- Mechanical thrombectomy has extended the therapeutic window, but combining it with neuroprotective strategies is the future.
- Nerinetide has shown promise in reducing infarct size and improving outcomes in clinical trials.
Purpose of the Study:
- To review recent advancements in in vitro and in vivo stroke models.
- To highlight models that improve the accuracy and effectiveness of therapeutic strategy evaluation.
- To bridge the gap between preclinical research and clinical practice for stroke therapy development.
Main Methods:
- Review of in vitro models, including spheroids and organoids, for high-throughput drug screening.
- Analysis of advancements in in vivo preclinical mouse stroke models.
- Focus on models that mimic clinical realities in surgical procedures, post-surgical care, and functional assessment.
Main Results:
- Novel in vitro models incorporate diverse brain cell types for comprehensive drug screening.
- Enhanced in vivo models more accurately replicate clinical stroke scenarios and patient care.
- These improved models facilitate more reliable preclinical evaluation of neuroprotective agents.
Conclusions:
- Accurate preclinical models are crucial for developing effective stroke therapies.
- Integrating functional outcome assessments in preclinical studies is essential for clinical translation.
- Future stroke treatment likely involves a combination of reperfusion and brain-protective strategies evaluated through advanced models.
Related Concept Videos
Ischemic Stroke l: Introduction
Ischemic stroke is an acute cerebrovascular condition in which blood flow to a brain region is suddenly interrupted, leading to tissue infarction. Neurons depend on continuous oxygen and glucose supply, so even brief reductions in perfusion cause energy failure, ionic imbalance, and irreversible injury. Ischemic strokes are classified into thrombotic and embolic types based on their underlying mechanisms.Thrombotic MechanismsThrombotic stroke develops when a clot forms within a cerebral artery.
Ischemic Stroke ll: Pathophysiology
An ischemic stroke occurs when a cerebral blood vessel becomes obstructed, most often by a thrombus or embolus, interrupting the delivery of oxygen and glucose to brain tissue. Because neurons rely on continuous aerobic metabolism, energy failure begins within minutes of reduced perfusion. The region receiving the least blood flow becomes the infarct core, an area of irreversible cellular death. Surrounding this core lies the penumbra, a zone of hypoperfused but still viable tissue that is...

