LDIR treatment induces axonal sprouting, brain rewiring, and EEG oscillatory activity two months after ischemic stroke. (A) In X-ray irradiated mice, a significant portion of axonal projections crossed the midline into the contralesional motor cortex. (B and C) Three-dimensional reconstruction of individual axonal projections revealed a significant number of neuronal projections in X-ray irradiated mice two months after stroke. (D) EEG signals were recorded simultaneously in injured (red circle) and uninjured (yellow circle) cortices in freely moving mice. (E) EEG activity was barely detectable in sham-irradiated mice two months after ischemic stroke. In contrast, brain activity significantly increased in mice irradiated with X-rays. Credit: Brain, behavior and immunity (2023). DOI: 10.1016/j.bbi.2023.09.015
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), such as X-ray irradiation, can reduce the size of lesions and reverse the motor deficits in TBI and ischemic stroke mice, demonstrating that LDIR could be a promising therapeutic strategy for patients with head trauma and stroke.
The results were published in Brain, behavior and immunity under the title “Low-dose ionizing radiation promotes motor recovery and brain rewiring by resolving the inflammatory response after brain injury and stroke.” »
Nearly half of traumatic brain injury and stroke survivors suffer lifelong motor impairment and disability. “Usually, secondary brain injuries worsen over time after primary injuries related to head trauma (mechanical insults such as a car accident or falls in the elderly) 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. “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 irradiation can enhance adaptive responses, including extending average lifespan, boosting the immune system, healing wounds, and stimulating cell growth in animals, as well as in neuroprotection in animal models of neurodegenerative diseases, mainly due to immunomodulation. Based on these studies, Professor Ma and his team hypothesized that the immunomodulatory effects of LDIR may play a central role in mitigating damage and promoting wound healing after brain injury.
In their study, they found that low-dose X-ray irradiation completely reversed motor deficits in TBI and stroke mice and restored brain activity after stroke. More importantly, low-dose X-ray irradiation treatment delayed for eight hours was still effective in achieving full recovery of motor function after stroke, which is clinically very relevant for translation of results into clinical applications, as this is most likely to occur in clinical settings, where hours may pass before a treatment is available.
Mice were treated with whole-body X-ray irradiation after cortical injury or photothrombotic ischemic stroke, while the control group of mice did not receive any (sham) irradiation. Seven days after cortical stab injury, X-ray irradiated mice showed a reduction in lesion size by 48%.
Magnetic resonance imaging showed that X-ray irradiation significantly reduced the infarct volume of stroke mice by 43 to 51% during the first week after induction. an ischemic stroke. These results support a common clinical observation that stroke patients with lower infarct volume generally have better clinical outcomes.
LDIR accelerates wound closure after ischemic stroke in adult mice. (A) Immediately after ischemic stroke induction, mice received a single exposure to sham irradiation as a control or LD X-ray irradiation at 300 mGy. (B and C) Infarct volume (black dashed line) was markedly reduced in mice irradiated with X-ray (300 mGy) at 1 and 3 dpi. (D) Magnetic resonance imaging (MRI) to monitor cerebral infarction of the same animal during recovery. (E) MRI confirmed a significant reduction in mean infarct volume (red dotted line in D) in X-ray irradiated mice. Credit: Brain, behavior and immunity (2023). DOI: 10.1016/j.bbi.2023.09.015
Furthermore, X-ray irradiation accelerated the substantial recovery of motor function detected by narrow-beam walking, pole climbing, and grip strength after cortical injury and ischemic stroke. For example, the X-ray irradiated mice took significantly less time to cross a narrow beam, with fewer foot slips, indicating that the time after cortical injury and ischemic stroke.
The team also conducted a 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, as well as downregulation of key pro-inflammatory cytokine production. This suggests that LDIR treatment has a strong immunomodulatory effect through the expression of genes involved in inflammatory and immune responses.
Most strikingly, their study demonstrated that LDIR promoted axonal projections (brain rewiring) in the motor cortex and recovery of brain activity detected by electroencephalography recordings months after a stroke. Although LDIR treatment was delayed for eight hours after injury, it still retained its full therapeutic effect on motor recovery.
“Our results indicate that LDIR is a promising therapeutic strategy for patients with head trauma and stroke,” said Professor Ma. “X-ray irradiation equipment for medical use is commonly available in all major hospitals. We believe this strategy could be used to address unmet medical needs by accelerating the restoration of motor function within a limited therapeutic window after severe brain injury, such as traumatic brain injury and stroke, providing a rationale for further clinical studies for a potential treatment strategy for patients.
More information:
Ngan Pan Bennett Au et al, Low-dose ionizing radiation promotes motor recovery and brain rewiring by resolving the inflammatory response after brain injury and stroke, Brain, behavior and immunity (2023). DOI: 10.1016/j.bbi.2023.09.015
Provided by City University of Hong Kong
Quote: Neuroscientists discover therapeutic potential of low-dose ionizing radiation for head trauma and ischemic stroke (January 26, 2024) retrieved January 26, 2024 from
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