Long-Term Neuroprotective Effects of Hydrogen-Rich Water and Memantine in Chronic Radiation-Induced Brain Injury: Behavioral, Histological, and Molecular Insights
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals and Ethics Statement
2.2. Animal Grouping and Treatment
2.3. Animal Irradiation Conditions
2.4. Timeline and Data Collection
2.5. Behavioral Experiments
2.6. Histopathological Evaluation
2.7. 18F-FDG PET/CT Static Imaging and Data Reconstruction Analysis
2.8. Oxidative Stress Biomarker Assessment
2.9. Transcriptomic Sequencing of Hippocampal Tissue
2.10. Real-Time Quantitative PCR (RT-qPCR) Analysis
2.11. Western Blotting Analysis
2.12. Rat Serum ELISA Detection
2.13. Statistical Analysis
3. Results
3.1. General Conditions of Animals
3.2. Behavioral Results
3.2.1. Open Field Test on Day 30 Post-Irradiation
3.2.2. Y-Maze Spontaneous Alternation Test on Day 31 Post-Irradiation
3.2.3. Novel Object Recognition Test on Days 32–33 Post-Irradiation
3.2.4. Open Field Test on Day 60 Post-Irradiation
3.2.5. Y-Maze Novel Arm Exploration Test on Day 61 Post-Irradiation
3.2.6. Morris Water Maze Test on Days 63 to 70 Post-Irradiation
3.2.7. Y-Maze Spontaneous Alternation Test on Day 73 Post-Irradiation
3.3. Histopathological Findings
3.3.1. HE Staining
3.3.2. BrdU + NeuN Immunofluorescence Double Labeling
3.3.3. Transmission Electron Microscopy (TEM) Analysis
3.3.4. Golgi Staining
3.3.5. Nissl Staining
3.4. 18F-FDG PET/CT Brain Static Imaging and Data Reconstruction Analysis
3.5. Oxidative Stress Markers
3.6. Transcriptomic Findings in the Hippocampus
3.6.1. Screening of Differentially Expressed Genes (DEGs)
3.6.2. GO Enrichment Analysis of Differentially Expressed Genes
3.6.3. KEGG Enrichment Analysis of Differentially Expressed Genes
3.6.4. Gene Set Enrichment Analysis (GSEA)
3.6.5. Protein–Protein Interaction (PPI) Network Analysis
3.7. Real-Time Quantitative PCR Validation of Key Protein-Related Gene Expression
3.8. Western Blot Analysis
3.9. Serum ELISA Biomarker Detection
4. Discussion
4.1. Behavioral Improvements by HRW in Chronic RIBI
4.2. Histopathological Analysis of HRW’s Protective Effects
4.3. Regulation of Oxidative Stress and Inflammation by HRW
4.4. Transcriptomic Analysis Reveals Potential Molecular Mechanisms
4.5. Pathway Analysis: Exploring the Mechanisms of HRW
4.6. Preliminary Exploration of Early Biomarkers for Chronic RIBI
4.7. Study Limitations and Translational Considerations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Day | Trial 1 | Trial 2 | Trial 3 | Trial 4 |
---|---|---|---|---|
1 | S | W | NW | SE |
2 | NW | S | SE | W |
3 | SE | NW | W | S |
4 | W | SE | S | NW |
5 | S | NW | W | SE |
6 & 8 (Probe) | SW |
Gene Name | Accession Number | Primer (5′ to 3′) | Product Length |
---|---|---|---|
Cd44 | NM_012924.3 | Forward primer: TCGATTTGAATATAACCTGCCG Reverse primer: CAGTCCTGGAGATACTGTAGC | 78 |
Cd74 | XM_006254761.4 | Forward primer: CACCCAGACTCCACCTAAAGTATT Reverse primer: TCTCATCACACTTGGGACGG | 98 |
Cd3e | NM_001108140.2 | Forward primer: CCAGACTATGAGCCCATCCG Reverse primer: TAGGATGCGTGTTCACCAGG | 178 |
RT1-Ba | NM_001008831.3 | Forward primer: TCCCCGAGTTTGGACAACTG Reverse primer: GTCGCCTCAGGAACCTTGTT | 133 |
RT1-Da | NM_001008847.2 | Forward primer: CTGTGAGATACCAGGAGGTGATG Reverse primer: AGGGGTATCCTCAGATGCTGT | 79 |
Spp1 | NM_012881.2 | Forward primer: GCCAGCCAAGGACCAACTAC Reverse primer: AGTGTTTGCTGTAATGCGCC | 133 |
Adipoq | NM_144744.3 | Forward primer: AATCCTGCCCAGTCATGAAG Reverse primer: TCTCCAGGAGTGCCATCTCT | 159 |
Kif18a | NM_001137642.1 | Forward primer: TGCCTTAGCAGATACAAAGAGAAGA Reverse primer: GTCTTTGGCACGATTTGCGT | 184 |
Gapdh | NM_017008.4 | Forward primer: CCGCATCTTCTTGTGCAGTG Reverse primer: CGATACGGCCAAATCCGTTC | 79 |
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Xu, K.; Liu, H.; Wang, Y.; He, Y.; Liu, M.; Lu, H.; Wang, Y.; Niu, P.; Qin, X. Long-Term Neuroprotective Effects of Hydrogen-Rich Water and Memantine in Chronic Radiation-Induced Brain Injury: Behavioral, Histological, and Molecular Insights. Antioxidants 2025, 14, 948. https://doi.org/10.3390/antiox14080948
Xu K, Liu H, Wang Y, He Y, Liu M, Lu H, Wang Y, Niu P, Qin X. Long-Term Neuroprotective Effects of Hydrogen-Rich Water and Memantine in Chronic Radiation-Induced Brain Injury: Behavioral, Histological, and Molecular Insights. Antioxidants. 2025; 14(8):948. https://doi.org/10.3390/antiox14080948
Chicago/Turabian StyleXu, Kai, Huan Liu, Yinhui Wang, Yushan He, Mengya Liu, Haili Lu, Yuhao Wang, Piye Niu, and Xiujun Qin. 2025. "Long-Term Neuroprotective Effects of Hydrogen-Rich Water and Memantine in Chronic Radiation-Induced Brain Injury: Behavioral, Histological, and Molecular Insights" Antioxidants 14, no. 8: 948. https://doi.org/10.3390/antiox14080948
APA StyleXu, K., Liu, H., Wang, Y., He, Y., Liu, M., Lu, H., Wang, Y., Niu, P., & Qin, X. (2025). Long-Term Neuroprotective Effects of Hydrogen-Rich Water and Memantine in Chronic Radiation-Induced Brain Injury: Behavioral, Histological, and Molecular Insights. Antioxidants, 14(8), 948. https://doi.org/10.3390/antiox14080948