Table 6.
Summary of key evidence supporting emerging research frontiers (burst keywords).
| Burst keyword (strength, period) | Key supporting references (examples) | Study models | Major findings/mechanistic insights | Potential therapeutic implication |
|---|---|---|---|---|
| Microglia polarization (15.28, 2019–2024)) | 6. Li Y, et al Neural Regen Res. 2025 22. Li F, et al Metab Brain Dis. 2018 |
In vitro BV2/HMC3 cells; Rodent MCAO model | Microglia shift from pro-inflammatory M1 (iNOS+, CD86+) to antiinflammatory/reparative M2 (Arg1+, CD206+) phenotype poststroke. M1 exacerbates injury via ROS/TNF-α; M2 promotes repair via BDNF/TGF-β. Phenotype is spatiotemporally dynamic. | Pharmacological (e.g., L-3-n-butylphthalide) or genetic modulation to promote M2 polarization. |
| NLRP3 inflammasome (16.81, 2020–2024) | 6. Li Y, et al Neural Regen Res. 2025 33. Ding J, et al Cell. 2017 34. Yang Y, et al Cell Death Dis. 2019 |
In vitro priming + activation assays; Rodent MCAO model; NLRP3 knockout mice | A multiprotein complex activated by DAMPs (e.g., K + efflux, mtDNA). Leads to Caspase-1 activation, IL-1β/IL-18 maturation, and pyroptosis (GSDMD cleavage), driving secondary inflammation. | Specific small-molecule inhibitors (e.g., MCC950) show neuroprotection in preclinical models. |
| Extracellular vesicles (16.84, 2020–2024) | 53. Zhang Q, et al J Nanobiotechnol. 2025 51. Song Y, et al Theranostics. 2019 52. Song Y, et al Stroke. 2023 |
In vitro cell co-culture; Rodent MCAO model with EV injection; Human plasma samples | EVs (especially from M2 microglia) carry miRNAs (e.g., miR-124, miR-25-3p) and proteins that modulate neuroinflammation, promote NSC differentiation, and protect the BBB. Act as intercellular communicators. | Engineered EVs as natural nanocarriers for drug/miRNA delivery (“cell-free therapy”). Diagnostic biomarkers. |
Arg1 = arginase 1, BBB = blood-brain barrier, BDNF = brain-derived neurotrophic factor, DAMPs = damage-associated molecular patterns, EVs = extracellular vesicles, GSDMD = Gasdermin D, IL = interleukin, iNOS = inducible nitric oxide synthase, MCAO = middle cerebral artery occlusion, NLRP3 = NLR family pyrin domain containing 3, NSC = neural stem cell, IS = ischemic stroke, ROS = reactive oxygen species, TNF-α = tumor necrosis factor-alpha, TGF-β = transforming growth factor beta.