Graphical AbstractImproving translation of tMCAO mice model. Improvement of the surgical procedure, post-operative care and functional evaluation in the tMCAO mice, gives rise to a model with high parallel and translation into clinical reality. Induction of ischemia for 45-mins using smaller commercial filaments gives rise to uniform lesion volume that together with the improved post-operative care, decreases this model mortality. Furthermore, this allows for intensive long-term functional evaluation of mice. This way, clinical symptoms and ethology, as well as scales used to evaluate stroke, are mimicked in a mouse model.
Ischemic stroke is a leading cause of death worldwide, mainly in western countries. So far, approved therapies rely on reperfusion of the affected brain area, by intravenous thrombolysis or mechanical thrombectomy. The last approach constitutes a breakthrough in the field, by extending the therapeutic window to 16–24 h after stroke onset and reducing stroke mortality. The combination of pharmacological brain-protective strategies with reperfusion is the future of stroke therapy, aiming to reduce brain cell death and decrease patients’ disabilities. Recently, a brain-protective drug—nerinetide—reduced brain infarct and stroke mortality, and improved patients’ functional outcomes in clinical trials. The success of new therapies relies on bringing preclinical studies and clinical practice close together, by including a functional outcome assessment similar to clinical reality. In this review, we focused on recent upgrades of in vitro and in vivo stroke models for more accurate and effective evaluation of therapeutic strategies: from spheroids to organoids, in vitro models that include all brain cell types and allow high throughput drug screening, to advancements in in vivo preclinical mouse stroke models to mimic the clinical reality in surgical procedures, postsurgical care, and functional assessment.
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