Longitudinal Neuropathological Consequences of Extracranial Radiation Therapy in Mice

Int. J. Mol. Sci., 2024 · DOI: 10.3390/ijms25115731 · Published: May 24, 2024

Simple Explanation

Cancer-related cognitive impairment (CRCI) can result from extracranial radiation therapy (ECRT). This study in mice explores how ECRT affects the brain and spinal cord over time. Mice received different doses of radiation to induce varying levels of skin reaction. Researchers then analyzed brain and spinal cord tissue for changes at different time points. The study found that ECRT caused changes in gene expression, protein levels, and activation of certain cells in the brain and spinal cord, suggesting potential pathways involved in CRCI.

Study Duration

25 days

Participants

SKH1 mice

Evidence Level

Not specified

Key Findings

1
ECRT induces dose-dependent changes in gene and protein expression in the brain, affecting neurotransmission, glial cell activation, and immune signaling.
2
ECRT leads to astrocyte activation in the thoracic spinal cord, with a delayed response observed at higher radiation doses.
3
Specific proteins associated with neuroinflammation and neurodegenerative diseases, such as MHCII, are upregulated in the striatum, retrosplenial cortex, and hippocampus following ECRT.

Research Summary

This study investigates the neuropathological consequences of extracranial radiation therapy (ECRT) in mice, focusing on the brain and spinal cord changes following radiation exposure to the hindlimb. The research reveals dose-dependent changes in protein and gene expressions in the brains of mice following ECRT, affecting pathways related to neurotransmission, glial cell activation, and immune signaling. The findings suggest that ECRT induces neuroinflammation and glial cell activation in the brain and spinal cord, providing potential signaling pathways for mitigation strategies against cancer-related cognitive impairment (CRCI).

Practical Implications

Mitigation Strategies for CRCI

The identification of specific signaling pathways involved in ECRT-related CRCI opens avenues for developing targeted therapies to mitigate cognitive impairment in cancer survivors.

Personalized Radiation Therapy

Understanding the dose-dependent effects of ECRT on the brain and spinal cord could lead to more personalized radiation therapy protocols that minimize neurotoxic side effects.

Biomarker Identification

The study's identification of specific proteins and genes altered in the brains of irradiated mice could serve as potential biomarkers for assessing the risk and severity of CRCI during and after cancer treatment.

Study Limitations

1
The mice were treated with a single, high-dose radiation treatment, which may not fully replicate the multi-fractionated radiation protocols used in human cancer treatment.
2
The sample size was small, potentially leading to type II errors and limiting the detection of subtle protein and gene expression changes.
3
Whole-brain hemisphere gene expression analysis may not capture regional gene expression changes within specific anatomical regions of the brain.

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