Low-Dose X-ray Irradiation Shows Promise in Treating Brain Injury

Traumatic brain injury (TBI) and ischemic stroke are major public health concerns and leading causes of death and disability worldwide. A research team led by City University of Hong Kong (CityU) neuroscientists recently discovered that low-dose ionizing radiation (LDIR), such as X-ray irradiation, can reduce lesion size and reverse motor deficits in TBI and ischemic stroke mice, demonstrating that LDIR may be a promising therapeutic strategy for TBI and stroke patients.

Nearly half of TBI and stroke survivors experience lifelong motor impairment and disability. “Usually, secondary brain damage worsens over time after primary injuries in TBI (mechanical insults such as a car accident or falls by older adults) and strokes (when blood flow to the brain is blocked), owing to the unfavorable and hostile neuroinflammatory environment in the brain,” explained Professor Eddie Ma Chi-him, in the Department of Neuroscience at CityU, who led the research. “But there is still no effective treatment for repairing the central nervous system after brain injury.”

Mice were treated with whole-body X-ray irradiation after cortical stab wound injury or photothrombotic ischemic stroke, while the control mouse group received no (sham) irradiation. Seven days after cortical stab wound injury, the X-ray-irradiated mice exhibited a reduction in lesion size by 48%. The magnetic resonance imaging showed that X-ray irradiation significantly reduced the infarct volume of stroke mice by 43–51% during the first week after the induction of ischemic stroke. These results support a common clinical observation that stroke patients with smaller infarct volume usually have improved clinical outcomes.

Moreover, X-ray irradiation accelerated substantial motor function recovery detected by narrow bean walking, pole climbing and grip strength after cortical stab wound injury and ischemic stroke. For instance, X-ray-irradiated mice took a much shorter time to transverse a narrow beam, with fewer foot slips, indicating that X-ray-irradiated mice demonstrated excellent motor coordination and balance shortly after cortical stab wound injury and ischemic stroke.

The team also conducted systems-level transcriptomic analysis, which showed that genes upregulated in LDIR-treated stoke mice were enriched in pathways associated with inflammatory and immune responses involving microglia. LDIR induced upregulation of anti-inflammatory- and phagocytosis-related genes, and downregulation of key pro-inflammatory cytokine production. This suggests that LDIR treatment has a strong immunomodulatory effect by the expression of genes involved in inflammatory and immune responses.

Reference: Au NPB, Wu T, Kumar G, et al. Low-dose ionizing radiation promotes motor recovery and brain rewiring by resolving inflammatory response after brain injury and stroke. Brain Behavior Immunity. 2024;115:43-63. doi: 10.1016/j.bbi.2023.09.015

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