Traumatic Brain Injury (TBI) and ischemic stroke are major public health problems, leading to the most common causes of death and disability worldwide. A research team led by neuroscientists at the City University of Hong Kong (CityU) has recently found 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, proving that LDIR could be a promising therapeutic strategy for TBI and stroke patients.
Almost half of the survivors of traumatic brain injury and stroke suffer lifelong motor impairments and disabilities. „Secondary brain damage usually worsens over time following primary injuries in TBI (mechanical assaults like a car accident or falls in older adults) and strokes (when blood flow to the brain is blocked) due to the unfavorable and hostile neuroinflammatory environment in the brain,“ explained Professor Eddie Ma Chi-him from the Department of Neuroscience at CityU, who led the research. „However, there is still no effective treatment to repair the central nervous system following a brain injury.“
It has long been known that low-dose X-ray irradiation can improve adaptive responses, including increasing average lifespan, stimulating the immune system, wound healing, and stimulating cell growth in animals, as well as providing neuroprotection in animal models of neurodegenerative diseases, mainly attributed to immunomodulation. Based on these studies, Professor Ma and his team speculated that the immunomodulatory effects of LDIR could play a crucial role in alleviating damage and promoting wound healing following a brain injury.
In their recent study, they found that low-dose X-ray irradiation completely reversed motor deficits in TBI and stroke mice and restored brain activity after a stroke. Furthermore, low-dose X-ray irradiation even with an eight-hour delayed treatment was still effective, allowing for a complete restoration of motor function after a stroke, a highly clinically relevant result that could likely happen in a clinical setting, where hours could pass before treatment is available.
Mice were treated with whole-body X-ray irradiation following a cortical stab injury or photothrombotic ischemic stroke, while the control group of mice received no (sham) irradiation. Seven days after the cortical stab wound, the irradiated mice showed a 48% reduction in lesion size. Magnetic resonance imaging showed that X-ray irradiation significantly reduced ischemic stroke mice’s infarct volume by 43-51% in the first week after inducing an ischemic stroke. These results support a common clinical observation that stroke patients with smaller infarct volumes generally achieve better clinical outcomes.
Moreover, X-ray irradiation accelerated significant recovery of motor functions, as evidenced by narrow beam walking, pole climbing, and grip strength following a cortical stab injury and ischemic stroke. For example, irradiated mice required much less time to traverse a narrow beam and were less likely to slip, suggesting that irradiated mice showed excellent motor coordination and balance shortly after a cortical stab wound and an ischemic stroke.
The team also conducted a transcriptomic analysis at the system level, which showed that the genes upregulated in LDIR-treated stroke mice were enriched in pathways associated with inflammatory and immune responses involving microglia. LDIR induced upregulation of anti-inflammatory and phagocytosis-related genes as well as downregulation of the production of key pro-inflammatory cytokines. This suggests that LDIR treatment has a strong immunomodulatory effect through the expression of genes involved in inflammatory and immune responses.
Even more notably, their study showed that LDIR promoted axonal projections (brain rewiring) in the motor cortex and restoration of brain activity, as evidenced by electroencephalography recordings months after stroke. Even when LDIR treatment was delayed by eight hours after injury, the full therapeutic effect on motor recovery remained.
Our findings suggest that LDIR is a promising therapeutic strategy for TBI and stroke patients. X-ray irradiation devices for medical purposes are generally available in all major hospitals. We believe that this strategy could be utilized to address unmet medical needs and accelerate the restoration of motor functions within a limited therapeutic window following severe brain injuries such as traumatic brain injury and stroke, justifying further clinical trials for a potential treatment strategy for patients.“
– Professor Eddie Ma Chi-him, Department of Neuroscience at CityU
The results have been published in Brain, Behavior, and Immunity under the title „Low-dose ionizing radiation promotes motor recovery and brain rewiring by resolving inflammatory responses following brain injuries and strokes.“
The lead author is Dr. Au Ngan-pan, a CityU doctoral student and currently a lecturer at the University of Portsmouth. The corresponding author is Professor Ma. Other CityU staff involved include Professor Kannie Chan Wai-yan and Professor Peter Yu Kwan-ngok, as well as doctoral 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 Special Administration Region, and the Shenzhen Science, Technology and Innovation Commission.
City University of Hong Kong
Au, NPB, et al. (2024). Low-dose ionizing radiation promotes motor recovery and brain rewiring by resolving inflammatory responses following brain injuries and strokes. Brain, Behavior, and Immunity. doi.org/10.1016/j.bbi.2023.09.015.