Radiation therapy (RT) remains a cornerstone in the treatment of brain cancers, yet its unintended consequence, radiation-induced cognitive dysfunction (RICD), affects up to 90% of survivors, profoundly diminishing quality of life.
A recent preclinical study published in Acta Neuropathologica Communications explored the potential of riluzole (RZ), an FDA-approved drug for amyotrophic lateral sclerosis (ALS), to counteract these cognitive impairments by augmenting brain-derived neurotrophic factor (BDNF).
BDNF is crucial for maintaining neuronal health, facilitating synaptic plasticity, and supporting cognitive functions including learning and memory. Studies have linked reduced BDNF levels to neurodegenerative disorders such as Alzheimer’s and Huntington’s diseases. In cancer patients, systemic chemotherapy and cranial RT have been shown to significantly lower BDNF levels, correlating with cognitive deficits.
Researchers used a mouse model to evaluate the effects of cranial RT (9 Gy) and subsequent RZ treatment. Key outcomes included cognitive assessments, BDNF quantification, and measures of neuroinflammation, synaptic integrity, and neurogenesis.
Mice receiving RT exhibited poor performance in memory and learning tasks. However, RZ-treated mice showed significant recovery, performing comparably to non-irradiated controls. RZ treatment restored hippocampal BDNF levels, which were reduced by RT by up to 53%. Elevated BDNF levels were associated with improved synaptic density and neuronal plasticity, the authors noted.
Synaptic markers such as synaptophysin and the immediate early gene product cFos were preserved in RZ-treated mice, underscoring the drug’s role in maintaining synaptic health. RT-induced neuroinflammation, characterized by activated microglia and astrogliosis, was significantly mitigated by RZ as well.
While RZ improved overall neuronal health and cognitive function, it did not reverse RT-induced loss of neurogenesis in the hippocampus. The authors wrote that this suggests that the benefits from RZ arise from enhancing existing neuronal networks rather than generating new neurons.
The study’s findings point to RZ as a potential neuroprotective agent to help preserve cognitive function and improve quality of life for patients receiving RT, the authors noted.
Given its established safety profile as an oral medication for ALS, RZ represents a promising and translationally feasible intervention for mitigating RICD. Further clinical trials will be essential to validate these preclinical findings and explore the broader application of RZ in cancer therapy-related cognitive impairment.
The authors declared no conflicts of interest.
