Photothrombotic Ischemic Stroke in Rats: A Systematic Review of Experimental Parameters and Therapeutic Applications in Neuroprotection, Neuromodulation, and Post-Stroke Recovery

Background/Objectives: This systematic review analyzed the experimental parameters of the photothrombotic ischemic stroke model in rats and their relationship with neuroprotection, neuromodulation, and post-stroke recovery studies. We examined the follow-up periods and the behavioral, histological, and complementary outcomes employed. Methods: The search was conducted in PubMed and Scopus following PRISMA guidelines. Of the 341 records identified, 34 studies met the eligibility criteria. Results: Sprague–Dawley, male, and young adult rats predominated, while Rose Bengal was used in all studies. Intravenous administration and transcranial irradiation without craniotomy were the most frequent approaches, with predominantly unilateral lesions targeting motor and sensorimotor regions. Despite this relative uniformity, the considerable variability in irradiation parameters and incomplete reporting of relevant physical characteristics of the protocols were observed, indicating limitations to interlaboratory reproducibility. Post-stroke recovery was the most frequent application, followed by neuromodulation and neuroprotection. Neuroprotection studies were concentrated in earlier time windows and combined a functional assessment with the characterization of lesion, neuronal survival, cell death, oxidative stress, and inflammation. Neuromodulation studies showed greater diversity in stimulation strategies and integrated behavioral outcomes with cellular, neurovascular, perfusion, neuroimaging, and electrophysiological assessments, supporting the investigation of circuit modulation. In contrast, recovery studies employed longer follow-up periods, with greater emphasis on dexterity, asymmetry, and motor performance, associated with assessments of neurogenesis, angiogenesis, neurotrophic factors, and neuronal reorganization. Conclusions: Overall, the findings demonstrate that neuroprotection, neuromodulation, and post-stroke recovery require distinct temporal windows and assessment strategies, and that the integrated selection of induction parameters and outcomes should be guided by the therapeutic purpose to improve the consistency and comparability of studies using the photothrombotic model.