Radiation-Induced Brain Injury: Mechanistic Insights and the Promise of Gut–Brain Axis Therapies

Brain Sci., 2024 · DOI: 10.3390/brainsci14121295 · Published: December 23, 2024

Simple Explanation

Radiation therapy is effective for craniofacial neoplasms but carries risks, including harm to neural structures, potentially causing focal cerebral necrosis or cognitive compromise. Evaluating post-treatment quality of life is crucial. This review explores treatments for radiation-induced cerebral injury, focusing on gut microbiota modulation. Radiation-induced brain injury (RIBI) can manifest acutely (within six weeks), subacutely (six weeks to six months), or late (months to years post-radiotherapy). Late injuries are progressive and irreversible, impacting patients’ quality of life. Precise mechanisms remain elusive. RIBI is a multistage phenomenon involving vascular compromise, glial cell damage causing neuroinflammation, cellular senescence, and dysregulation of neural stem cell functionality. Recent studies suggest the gut microbiota's involvement in neurologic pathologies.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Immunotherapy combined with SRS shows the highest incidence of radiation necrosis (RN) or tumor-related imaging changes compared to targeted therapy and chemotherapy, suggesting a significant correlation between immunotherapy and increased RN rates.
2
A cumulative radiation dose exceeding 75.7 Gy is a critical factor in RIBI in patients treated for lung cancer brain metastases.
3
The gut microbiota influences neurodevelopment and inflammation, with maternal microbiota deficiencies potentially impairing embryonic axonal development and affecting offspring’s sensory behaviors.

Research Summary

This review explores radiation-induced brain injury (RIBI), its causes, and potential treatments, with a focus on the gut–brain axis as a therapeutic strategy. RIBI is influenced by treatment, tumor, and patient-specific factors. Treatment-associated factors include immunotherapy, targeted therapy, chemotherapy and radiotherapy techniques. Preventive and therapeutic measures include hippocampal avoidance radiotherapy, hypofractionated stereotactic radiotherapy, medications like bevacizumab and glucocorticoids, and physical therapies like hyperbaric oxygen therapy.

Practical Implications

Radiotherapy Planning Optimization

Minimize V12 Gy in radiotherapy planning to mitigate potential adverse outcomes when integrating radiotherapy with immunotherapeutic interventions.

Early RIBI Treatment

Initiating treatment within three months of the initial RIBI diagnosis can significantly reduce the likelihood of death.

Gut Microbiota Modulation

Targeting the gut microbiota represents an innovative strategy for treating RIBI, requiring further research to validate and identify effective modulation methods.

Study Limitations

1
Limited understanding of radiation effects on the elderly due to their exclusion from clinical trials.
2
Conclusive evidence regarding the impact of re-radiotherapy on RIBI remains elusive.
3
Most investigations on the connection between imbalanced gut microbiota and RIBI rely heavily on mouse models.

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