Low-dose radiation shows promise as treatment for brain injury and stroke

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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 (CTU) neuroscientists recently discovered that low-dose ionizing radiation (LDIR), such as X-ray radiation, can reduce lesion size and reverse motor deficits in TBI and ischemic stroke mice, demonstrating that that LDIR may be a promising therapeutic strategy for TBI and stroke patients.

About half of TBI and stroke survivors experience lifelong motor impairment and disability. “In general, secondary brain damage worsens over time after primary trauma (mechanical insults such as car accidents or falls by the elderly) and stroke (when blood flow to the brain is cut off) in TBI due to an adverse and hostile neuroinflammatory environment. Brain ,” explained Professor Eddie Ma Chi-him of CTU’s Department of Neuroscience, who led the research. “But there is still no effective treatment to repair the central nervous system after brain injury.”

It has long been known that low-dose X-ray radiation can enhance adaptive responses, including extending life expectancy, stimulating the immune system, healing wounds, and stimulating cell growth in animals, as well as neuroprotection in animal models of neurodegenerative diseases. to immunomodulation. Based on this research, Professor Ma and his team hypothesized that the immunomodulatory effects of LDIR may play an important role in reducing damage and wound healing after brain injury.

In their recent study, they found that low-dose X-ray radiation completely reversed motor deficits in TBI and stroke rats and restored brain activity after stroke. More importantly, low-dose X-ray radiation treatment delayed for eight hours was still effective in allowing full recovery of motor function after stroke, which is highly clinically relevant in translating the results into clinical applications, since it is very likely. Can occur in clinical settings, where hours may pass before any treatment is available.

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

Furthermore, X-ray radiation accelerates the recovery of motor function as detected by narrow bin walking, pole climbing and grip strength after cortical stab injury and ischemic stroke. For example, X-ray-irradiated rats took significantly less time to transverse a narrow beam, with less foot slip, indicating that X-ray-irradiated rats exhibit excellent motor coordination and balance only after cortical stab injury and ischemic stroke.

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

More surprisingly, their study showed that LDIR promoted axonal projections to the motor cortex (brain regeneration) and restored brain activity detected by electroencephalography recordings several months after stroke. Even if LDIR treatment is delayed eight hours after injury, it still maintains full therapeutic effect on motor recovery.

Our findings indicate that LDIR is a promising therapeutic strategy for TBI and stroke patients. X-ray radiation equipment for medical use is generally available in all major hospitals. We believe this strategy can be used to address unmet medical needs to accelerate motor function recovery within a limited therapeutic window after severe brain injuries such as TBI and stroke, warranting further clinical research for a potential treatment strategy for patients.”


Professor Eddie Ma Chi-him, Department of Neuroscience, CTU

Results are published Brain, behavior and immunity Under the title “Low-dose ionizing radiation promotes motor recovery and brain recycling by resolving the inflammatory response after brain injury and stroke.”

The first author is Dr Au Ngan-Pan, a CTU PhD graduate and currently a lecturer at the University of Portsmouth. Corresponding author Prof. Ma. Other CTU collaborators include Professor Kenny Chan Wai-Yan and Professor Peter U Kwan-Ngok, and PhD 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.

Source:

Journal Reference:

Au, NPB, etc. (2024). Low-dose ionizing radiation promotes motor recovery and brain recovery by resolving the inflammatory response after brain injury and stroke. Brain, behavior and immunity. doi.org/10.1016/j.bbi.2023.09.015.



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