Pharmacodynamic Effects of Standard versus High Caffeine Doses in the Developing Brain of Neonatal Rats Exposed to Intermittent Hypoxia
Abstract
:1. Introduction
2. Results
2.1. Blood Gases
2.2. Growth
2.3. Histopathology
2.4. Oxidative Stress and Apoptosis
2.5. Immunoreactivity
2.6. Myelination
3. Discussion
4. Materials and Methods
4.1. Experimental Design
4.2. Justification for the Doses of Caffeine
4.3. Intermittent Hypoxia Profile
4.4. Sample Collection
4.5. 8-isoPGF2α, PGF2α and 8-OHdG
4.6. Caspase-3 and -9
4.7. Total Cellular Protein Levels
4.8. Histopathology
4.9. Myelin Stain
4.10. Golgi Staining
4.11. Morphometric Analyses
4.12. Immunofluorescence (IF) Staining
4.13. Statistical Analyses
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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Groups | pH | PCO2 | PO2 | SO2 |
---|---|---|---|---|
RA: | ||||
Saline | 7.593 ± 0.03 | 31.1 ± 1.9 | 83.3 ± 7.9 | 97.5 ± 0.65 |
LoC | 7.526 ± 0.01 | 34.0 ± 0.42 | 69.0 ± 5.6 | 96.0 ± 0.87 |
HiC | 7.568 ± 0.03 | 31.7 ± 1.8 | 122.5 ± 22.5 | 98.8 ± 0.48 |
50% O2: | ||||
Saline | 7.584 ± 0.006 | 37.5 ± 0.49 * | 130.5 ± 6.5 ** | 99.3 ± 0.18 * |
LoC | 7.58 ± 0.013 # | 39.1 ± 1.14 ## | 115.5 ± 11.5 ## | 98.5 ± 0.61 # |
HiC | 7.523 ± 0.017 §§ | 41.8 ± 0.79 ‡§§ | 88.8 ± 12.7 § | 97.0 ± 0.91 § |
Neonatal IH: | ||||
Saline | 7.562 ± 0.037 | 34.9 ± 2.4 | 94.0 ± 4.7 | 98.0 ± 0.41 |
LoC | 7.528 ± 0.02 | 38.6 ± 1.2 ## | 101.5 ± 12.3 | 98.0 ± 0.71 |
HiC | 7.55 ± 0.026 | 37.8 ± 1.0 ‡ | 93.5 ± 20.1 | 96.8 ± 1.5 |
Groups | Total Brain Width (µm) | Layer 1 Width (µm) | Layer 2 Width (µm) |
---|---|---|---|
RA: | |||
Saline | 6161.5 ± 98.1 | 129.7 ± 3.6 | 55.0 ± 2.1 |
LoC | 8534.4 ± 69.5 ** | 130.7 ± 3.9 | 57.6 ± 1.6 |
HiC | 8216.7 ± 58.4 ** | 125.4 ± 7.3 | 101.0 ± 14.1 ** |
50% O2: | |||
Saline | 6864.6 ± 71.9 * | 134.9 ± 16.8 | 104.8 ± 16.1 * |
LoC | 9166.6 ± 194.1 ##§§ | 233.1 ± 11.6 ## | 119.1 ± 13.6 ## |
HiC | 7588.9 ± 51.6 | 114.9 ± 12.8 | 102.9 ± 11.6 |
Neonatal IH: | |||
Saline | 7240.9 ± 263.9 ** | 169.8 ± 17.9 | 120.0 ± 16.3 ** |
LoC | 7905.9 ± 62.5 ## | 147.5 ± 17.9 | 115.7 ± 15.4 ## |
HiC | 7009.2 ± 212.1 ‡ | 109.4 ± 14.8 † | 105.3 ± 14.2 |
Groups | Total No. Neurons (n = 20 Measurements/Group) | Dendritic LengthµM (n = 25 Measurements/Group) | No. Dendrites per Neuron (n = 25 Measurements/Group) |
---|---|---|---|
RA: | |||
Saline | 7.2 ± 0.29 | 22.3 ± 0.49 | 2.9 ± 0.2 |
LoC | 22.0 ± 0.43 ** | 21.9 ± 0.12 | 4.4 ± 0.02 ** |
HiC | 17.7 ± 0.36 ** | 12.8 ± 0.08 ** | 3.8 ± 0.18 ** |
50% O2: | |||
Saline | 0.1 ± 0.07 ** | 0.0 ± 0.0 ** | 0.0 ± 0.0 ** |
LoC | 2.5 ± 0.3 ##§§ | 0.04 ± 0.04 ## | 0.04 ± 0.04 ## |
HiC | 8.9 ± 0.26 ‡§§ | 0.02 ± 0.01 ‡ | 0.08 ± 0.06 ‡ |
Neonatal IH: | |||
Saline | 4.0 ± 0.25 ** | 9.9 ± 0.06 ** | 3.2 ± 0.16 |
LoC | 15.2 ± 0.34 ##§§ | 14.3 ± 0.12 ##§§ | 3.5 ± 0.20 ## |
HiC | 14.4 ± 0.23 ‡§§ | 11.9 ± 0.06 ‡§§ | 3.2 ± 0.16 ‡ |
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Soontarapornchai, K.; Cai, C.L.; Ahmad, T.; Aranda, J.V.; Hand, I.; Beharry, K.D. Pharmacodynamic Effects of Standard versus High Caffeine Doses in the Developing Brain of Neonatal Rats Exposed to Intermittent Hypoxia. Int. J. Mol. Sci. 2021, 22, 3473. https://doi.org/10.3390/ijms22073473
Soontarapornchai K, Cai CL, Ahmad T, Aranda JV, Hand I, Beharry KD. Pharmacodynamic Effects of Standard versus High Caffeine Doses in the Developing Brain of Neonatal Rats Exposed to Intermittent Hypoxia. International Journal of Molecular Sciences. 2021; 22(7):3473. https://doi.org/10.3390/ijms22073473
Chicago/Turabian StyleSoontarapornchai, Kutilda, Charles L. Cai, Taimur Ahmad, Jacob V. Aranda, Ivan Hand, and Kay D. Beharry. 2021. "Pharmacodynamic Effects of Standard versus High Caffeine Doses in the Developing Brain of Neonatal Rats Exposed to Intermittent Hypoxia" International Journal of Molecular Sciences 22, no. 7: 3473. https://doi.org/10.3390/ijms22073473