Low-dose ionising radiation may be promising therapeutic strategy in TBI and stroke – NeuroNews International

Eddie Chi-Him Ma (Credit: City University of Hong Kong)

A research team led by City University of Hong Kong (CityU; Kowloon, Hong Kong) neuroscientists recently discovered that low-dose ionising radiation (LDIR), such as X-ray irradiation, can reduce lesion size and reverse motor deficits associated with traumatic brain injury (TBI) and ischaemic stroke in mouse models. The researchers believe this demonstrates LDIR may be a promising therapeutic strategy for human TBI and stroke patients.

Our findings indicate that LDIR is a promising therapeutic strategy for TBI and stroke patients, said Eddie Chi-Him Ma (CityU, Kowloon, Hong Kong), who led this research endeavour. 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 in accelerating motor function restoration within a limited therapeutic window after severe brain injury, like TBI and stroke, warranting further clinical studies for a potential treatment strategy for patients.

A recent CityU news release details that nearly half of all TBI and stroke survivors experience lifelong motor impairment and disability, and, as such, both represent major public health concerns globally.

Usually, secondary brain damage worsens over time after primary injuries in TBI and strokes, owing to the unfavourable and hostile neuroinflammatory environment in the brain, Ma explained. But, there is still no effective treatment for repairing the central nervous system after brain injury.

As noted in the release, it has long been known that low-dose X-ray irradiation can enhance adaptive responses, including extending average life expectancy, stimulating the immune system, healing wounds, and stimulating cell growth in animals, as well as offering neuroprotection in animal models of neurodegenerative diseasesprimarily due to immunomodulation. Based on prior studies indicating this, Ma and his team speculated that the immunomodulatory effects of LDIR could play a pivotal role in mitigating damage and promoting wound healing after brain injury.

In their study, they found that low-dose X-ray irradiation completely reversed the motor deficits in mice with TBI and stroke, and restored brain activity after stroke. More importantly, CityUs release adds, low-dose X-ray irradiation treatment delayed by eight hours maintained a full therapeutic effect in allowing a complete recovery of motor function, as detected by electroencephalography recordings taken months after stroke. This is highly clinically relevant in the translation of these findings into real-world settings in whichdespite the time-sensitive nature of stroke therapyseveral hours may elapse before any treatment is available.

Some mice were treated with whole-body X-ray irradiation after cortical stab wound injury or photothrombotic ischaemic stroke in the study, while mice in a control 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%. Magnetic resonance imaging showed that X-ray irradiation significantly reduced the stroke infarct volume in these mice by 4351% during the first week after the induction of ischaemic stroke. The CityU release states that these results support the common clinical observation that stroke patients with smaller infarct volumes usually experience improved clinical outcomes.

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

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

The findings of this experimental study have been published in the journal Brain, Behavior, and Immunity.

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Low-dose ionising radiation may be promising therapeutic strategy in TBI and stroke - NeuroNews International