Animal Models for Long-Term Functional Recovery and Rehabilitation After Ischemic Stroke: Beyond Acute Neuroprotection

Summary

This review discusses the use of animal models in the study of long-term functional recovery and rehabilitation after ischemic stroke, with an emphasis on processes beyond acute neuroprotection.

Abstract

Ischemic stroke is one of the leading causes of long-term disability worldwide. Although acute neuroprotection strategies have been extensively studied, the mechanisms underlying long-term functional recovery after ischemic stroke remain incompletely understood. Animal models have played an important role in identifying key processes such as neural plasticity, angiogenesis, blood-brain barrier repair, and regulation of neuroinflammation during the recovery phase. These models enable the investigation of complex, time-dependent biological cascades that are difficult to examine directly in clinical studies. This narrative review discusses the application of animal models in studying long-term functional recovery after ischemic stroke. We highlight advances in understanding critical biological mechanisms, including axonal remodeling, neurogenesis, vascular repair, and immune modulation. Furthermore, we examine rehabilitation-oriented approaches evaluated in preclinical studies, such as stem cell therapy, neuromodulation techniques, pharmacological interventions, and environmental enrichment, and consider how mechanistic insights may inform their optimization. The integration of multimodal assessment methods-combining behavioral analyses, imaging, and molecular techniques-has strengthened the translational value of preclinical stroke recovery research. This narrative review provides a perspective on the development of mechanism-based rehabilitation strategies aimed at promoting sustained functional recovery beyond the acute phase of ischemic stroke. These insights help bridge the gap between preclinical research and clinical application and support improved outcomes for ischemic stroke survivors.

Introduction

Ischemic stroke is a leading cause of disability worldwide and imposes a substantial burden on patients, families, and healthcare systems^1,2,3. Despite advances in acute stroke therapies, including thrombolysis and mechanical thrombectomy, which have reduced mortality and limited initial brain injury, a considerable proportion of stroke survivors experience persistent long-term functional impairments⁴. These impairments commonly include motor deficits, cognitive dysfunction, and language disturbances, which severely reduce patients' autonomy and qu....