Animal Models for Studying Post-Stroke Neuroplasticity
Downloads
Ischemic stroke remains one of the leading causes of long-term disability worldwide, with recovery dependent on the brain's neuroplastic potential. This review aims to evaluate the role of animal models in elucidating the mechanisms of neuroplasticity following stroke and their relevance to clinical application. Using qualitative literature analysis, the study synthesizes findings from various animal models including rodents, non-human primates, zebrafish, and Drosophila. Rodent models, particularly the middle cerebral artery occlusion (MCAO), have been instrumental in identifying key processes such as BDNF-driven synaptic remodeling, VEGF-induced angiogenesis, and glial involvement in tissue repair. Additionally, systemic modulators like the gut-brain axis, immune responses, and extracellular vesicles are increasingly recognized for their influence on recovery. Despite these insights, most studies disproportionately utilize young, healthy male animals, limiting their relevance to diverse patient populations with comorbidities and aging factors. The findings suggest a need for integrative, multimodal research that incorporates molecular techniques, imaging, and behavioral assays, along with cross-species validation, to improve translational outcomes. This review underscores the necessity of leveraging a broader spectrum of animal models and advanced methodologies to develop effective, personalized therapies for post-stroke rehabilitation.
Badoiu, A., et al. (2023). Impact of transcranial magnetic stimulation on stroke recovery. *Neural Plasticity*, 2023, 1–23.
Balkaya, M., et al. (2013). Modeling post-stroke functional outcome in mice: improved predictive validity with a modified MCAO model. *Journal of Cerebral Blood Flow & Metabolism*, 33(6), 681–689.
Benakis, C., et al. (2016). Commensal microbiota affects ischemic stroke outcome by regulating intestinal gammadelta T cells. *Nature Medicine*, 22(5), 516–523.
Campbell, B. C. V., et al. (2019). Ischaemic stroke. *Nature Reviews Disease Primers*, 5(1), 70.
Carmichael, S. T. (2006). Cellular and molecular mechanisms of neural repair after stroke: making waves. *Annals of Neurology*, 59(5), 735–742.
Chauhan, A., et al. (2022). Omics approaches in stroke: progress and potential in preclinical and clinical research. *International Journal of Molecular Sciences*, 23(1), 341.
Chung, W. S., et al. (2015). Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. *Nature*, 504(7480), 394–400.
Cirillo, C., et al. (2020). Post-stroke remodeling processes in animal models and humans. *Journal of Cerebral Blood Flow & Metabolism*, 40(1), 3–22.
Clarkson, A. N., et al. (2010). Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke. *Nature*, 468(7321), 305–309.
Cook, D. J., et al. (2012). The use of nonhuman primates in research on recovery after stroke. *Journal of Cerebral Blood Flow & Metabolism*, 32(3), 463–475.
Dirnagl, U., et al. (2013). Improving translational research in stroke. *Stroke*, 44(6), 1764–1769.
Doeppner, T. R., et al. (2015). Extracellular vesicles improve post-stroke recovery by promoting neurogenesis and angiogenesis. *Stem Cells Translational Medicine*, 4(10), 1131–1143.
Feigin, V. L., et al. (2021). Global, regional, and national burden of stroke and its risk factors. *The Lancet Neurology*, 20(10), 795–820.
Fluri, F., et al. (2015). Animal models of ischemic stroke and their application in clinical research. *Drug Design, Development and Therapy*, 9, 3445–3454.
Hankey, G. J. (2017). Stroke. *The Lancet*, 389(10069), 641–654.
Hays, S. A., et al. (2020). Vagus nerve stimulation during rehabilitative training improves functional recovery after intracerebral hemorrhage. *Stroke*, 51(8), 2475–2483.
Heisenberg, M. (1998). What do the mushroom bodies do for the insect brain? *Learning & Memory*, 5(1-2), 1–10.
Hermann, D. M., et al. (2019). Opportunities and limitations of vascular risk factor models in studying plasticity-promoting and restorative ischemic stroke therapies. *Neural Plasticity*, 2019, 1–12.
Herson, P. S., & Traystman, R. J. (2014). Animal models of stroke: translational potential at present and in 2050. *Future Neurology*, 9(5), 541–551.
Howells, D. W., et al. (2010). Different stroke models reveal differences in neuroplasticity. *International Journal of Stroke*, 5(5), 386–393.
Iadecola, C., & Anrather, J. (2011). The immunology of stroke: from mechanisms to translation. *Nature Medicine*, 17(7), 796–808.
Joy, M. T., & Carmichael, S. T. (2021). Encouraging an excitable brain state: mechanisms of brain repair in stroke. *Nature Reviews Neuroscience*, 22(1), 38–53.
Jones, T. A., & Adkins, D. L. (2015). Motor system reorganization after stroke: stimulating and training toward perfection. *Physiology*, 30(5), 358–370.
Kizil, C., et al. (2012). Regeneration in zebrafish brain: genetic approaches and tools. *Current Opinion in Neurobiology*, 22(3), 500–508.
Labat-Gest, V., & Tomasi, S. (2013). Photothrombotic ischemia: a minimally invasive and reproducible photochemical cortical lesion model for mouse stroke studies. *Journal of Visualized Experiments*, (76), e50370.
Langhorne, P., et al. (2011). Stroke rehabilitation. *The Lancet*, 377(9778), 1693–1702.
Liddelow, S. A., et al. (2017). Neurotoxic reactive astrocytes are induced by activated microglia. *Nature*, 541(7638), 481–487.
Liu, Z., et al. (2021). STAT3 signaling is required for motor circuit function and neuronal integrity. *Brain Research*, 1750, 147162.
Longa, E. Z., et al. (1989). Reversible middle cerebral artery occlusion without craniectomy in rats. *Stroke*, 20(1), 84–91.
Ma, Q., et al. (2022). Gut microbiota contributes to neuroinflammation in ischemic stroke. *Frontiers in Cellular and Infection Microbiology*, 12, 841968.
Murphy, T. H., & Corbett, D. (2009). Plasticity during stroke recovery: from synapse to behaviour. *Nature Reviews Neuroscience*, 10(12), 861–872.
Roitbak, T. (2019). MicroRNAs and regeneration after brain injury. *Neural Plasticity*, 2019, 524412.
Scheneider, S. A., et al. (2019). SSRIs and stroke recovery: mechanisms and clinical implications. *Stroke*, 50(6), 1633–1640.
Schwarz, C., et al. (2020). Multimodal assessment for stroke recovery prediction. *Frontiers in Neurology*, 11, 628.
Sims, S. K., et al. (2022). Neurotrophic factors and post-stroke recovery. *Neural Plasticity*, 2022, 1–15.
Ueno, Y., et al. (2020). Cognitive impairment and neurobehavioral deficits in nonhuman primate models of stroke. *Experimental Neurology*, 330, 113332.
Ward, N. S., & Carmichael, S. T. (2020). Neural plasticity and recovery of function. *Handbook of Clinical Neurology*, 167, 283–300.
Wang, Y., et al. (2016). VEGF-B promotes recovery after stroke. *Cell Death & Disease*, 7(6), e2097.
Xin, H., et al. (2013). Systemic administration of exosomes derived from mesenchymal stem cells promotes functional recovery and neurovascular plasticity after stroke in rats. *Journal of Cerebral Blood Flow & Metabolism*, 33(11), 1711–1715.
Zhou, Y., et al. (2020). CRISPR-based genome editing in zebrafish for stroke research. *Developmental Biology*, 457(2), 121–130.
Copyright (c) 2025 Risdiansyah, Ahmad Ghiffari, Rury Tiara Oktariza, Fadhillah Putri Rusdi

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-ShareAlike 4.0 International (CC-BY-SA). that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.






