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Low-dose radiotherapy as an anti-inflammatory strategy in neonatal hypoxic-ischemic encephalopathy
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X. Du   , L. Luo |
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Abstract: (13 Views) |
Background: Neonatal hypoxic-ischemic encephalopathy (HIE) affects 1–26 per 1,000 live births, driving sustained neuroinflammation via NF-κB activation, microglial M1 polarization, and cytokine storms (TNF-α, IL-1β, IL-6), causing secondary brain injury and disability in 40–50% of hypothermia-treated survivors. However, it remains unknown whether low-dose radiotherapy (LDRT, ≤0.1 Gy) resolves this previously elusive cascade through ATM–IKK–NF-κB suppression and microglial repolarization in preclinical models. Materials and Methods: We systematically reviewed preclinical evidence on anti-inflammatory interventions in HIE, with focused synthesis of radiobiological studies using LDRT (≤0.1 Gy) across ischemic, neurodegenerative, and neuroinflammatory models (n > 15 independent reports). Results: LDRT demonstrated 3–6-fold suppression of TNF-α and IL-1β (P < 0.001, 95% CI 2.8–7.1, n = 12 models) through ATM-dependent IKK inhibition. It uncovered microglial M2 repolarization with 4-fold IL-10 and 3.5-fold TGF-β upregulation (P < 0.001). Combined with hypothermia, LDRT resolved previously inaccessible persistent inflammation, achieving 75–85% reduction in secondary injury biomarkers (oxidative stress, apoptosis; P < 0.001). Conclusion: LDRT establishes a radiobiological framework that transforms multimodal neonatal neuroprotection, opening the door to precision anti-inflammatory strategies that mitigate inflammation-driven brain injury in HIE. |
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| Keywords: Hypoxia-ischemia, brain, infant, newborn, inflammation, radiotherapy, neuroprotective agents, nf-kappa b, microglia. |
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Full-Text [PDF 799 kb]
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Type of Study: Review article |
Subject:
Radiation Biology
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