Traumatic brain injury (TBI) and ischemic stroke are major public health problems and leading causes of death and disability worldwide. A research team led by neuroscientists from the City University of Hong Kong (CityU) recently discovered that low-dose ionizing radiation (LDIR), corresponding to X-ray irradiation, can reduce the scale of lesions and reverse motor deficits in mice with TBI and ischemic stroke, which shows that LDIR could also be a promising therapeutic strategy for patients with TBI and stroke.

Nearly half of TBI and stroke survivors experience lifelong motor impairment and disability. “Typically, secondary brain damage worsens over time after primary injuries in TBI (mechanical injuries corresponding to automobile accidents or falls within the elderly) and strokes (when blood flow to the brain is blocked) attributable to an unfavorable and hostile neuroinflammatory environment within the body. brain,” explained Professor Eddie Ma Chi-him from the Department of Neuroscience at CityU, who led the research. “But there remains to be no effective strategy to repair the central nervous system after brain damage.”

It has long been known that low-dose X-ray irradiation can enhance adaptive responses, including extending life expectancy, stimulating the immune system, healing wounds, and stimulating cell growth in animals, and providing neuroprotection in an animal model of neurodegenerative diseases, primarily attributable to immunomodulation. Based on this research, Professor Ma and his team speculated that the immunomodulatory effects of LDIR may play a key role in mitigating damage and promoting wound healing after brain injury.

Of their recent study, they found that low-dose X-ray irradiation completely reversed motor deficits in mice with TBI and stroke and restored brain activity after stroke. More importantly, low-dose X-ray irradiation treatment delayed for eight hours was still effective in allowing complete recovery of motor function after stroke, which is extremely clinically relevant in translating the outcomes to clinical applications as it is vitally more likely to occur in clinical settings , where it might be hours before any treatment is out there.

Mice were treated with whole-body X-ray irradiation after cortical stab wound injury or photothrombotic ischemic stroke, while a control group of mice received no (sham) irradiation. Seven days after cortical stab wound injury, X-ray-irradiated mice showed a 48% reduction in lesion size. Magnetic resonance imaging showed that X-ray irradiation significantly reduced infarct volume in post-stroke mice by 43–51% in the primary week after induction of ischemic stroke. These results support the common clinical commentary that stroke patients with smaller infarct volumes are likely to have higher clinical outcomes.

Furthermore, X-ray irradiation accelerated significant recovery of motor function, as 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 significantly less time to traverse a narrow beam and had fewer foot slips, indicating that X-ray-irradiated mice exhibited excellent motor coordination and balance shortly after cortical damage and ischemic stroke.

The team also performed a systems-level transcriptomic evaluation, which showed that genes upregulated in LDIR-treated stoke mice were enriched in pathways related to microglia-mediated inflammatory and immune responses. LDIR induced upregulation of anti-inflammatory and phagocytosis-related genes and downregulation of key proinflammatory cytokine production. This means that LDIR treatment has a powerful immunomodulatory effect through the expression of genes involved in inflammatory and immune responses.

More strikingly, their study showed that LDIR promotes axonal projection (rewiring of brain connections) within the motor cortex and restoration of brain activity detected in electroencephalographic recordings several months after stroke. Even when LDIR treatment was delayed for eight hours after injury, it still retained its full therapeutic effect on motor recovery.

Our findings indicate that LDIR is a promising therapeutic strategy for patients with TBI and stroke. X-ray irradiation equipment for medical use is widely available in all major hospitals. We imagine this strategy could be used to handle the unmet medical must speed up recovery of motor function inside a limited therapeutic window following severe brain injury corresponding to TBI and stroke, warranting further clinical trials to ascertain a possible treatment strategy for patients.”

Professor Eddie Ma Chi-him from the Department of Neuroscience at CityU

The outcomes were published in Brain, behavior and immunity titled “Low doses of ionizing radiation support motor regeneration and brain remodeling by eliminating the inflammatory response after brain injury and stroke.”

The primary creator is Dr Au Ngan-pan, a CityU PhD graduate and currently a lecturer on the University of Portsmouth. The corresponding creator is Professor Ma. Other CityU collaborators include Professor Kannie Chan Wai-yan and Professor Peter Yu Kwan-ngok, and graduate students Wu Tan and Joseph Lai Ho-chi. The research was supported by the General Research Fund of the Research Grants Council, the Health and Medical Research Fund of the Food and Health Bureau of the Hong Kong SAR Government, and the Shenzhen Science, Technology and Innovation Commission.