Carvacrol Inhibits Expression of Transient Receptor Potential Melastatin 7 Channels and Alleviates Zinc Neurotoxicity Induced by Traumatic Brain Injury
Abstract
:1. Introduction
2. Results
2.1. Carvacrol Treatment Attenuated Over-Expression of TRPM7 and Accumulation of Free Zinc in the Hippocampal Neurons after TBI
2.2. Carvacrol Treatment Reduced TBI-Induced Neuronal Injury
2.3. Carvacrol Treatment Reduced TBI-Induced Oxidative Stress
2.4. Carvacrol Treatment Reduced TBI-induced Microglial Activation
2.5. Carvacrol Treatment Improved Neurological Impairment and Reduced Neuronal Death after TBI
2.6. 2-APB or NS8593 Treatment Reduced TRPM7 Over-expression, Free Zinc Accumulation, and Neuronal Injury after TBI
3. Discussion
4. Materials and Methods
4.1. Ethical Statement and Experimental Animals
4.2. Controlled Cortical Impact for TBI
4.3. Drug Treatment and Experimental Design
4.4. Zinc Staining
4.5. Tissue Preparation
4.6. Evaluation of Hippocampal Degenerating Neurons
4.7. Immunohistochemistry
4.8. Immunofluorescence Analysis
4.9. Modified Neurological Severity Score
4.10. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Time Point | Modified NSS | TBI-Vehicle | TBI-Carvacrol | p-Value |
---|---|---|---|---|
1 h | Motor tests | 4.0 ± 0.45 | 4.2 ± 0.37 | |
Sensory tests | 1.2 ± 0.2 | 1.6 ± 0.24 | ||
Beam balance tests | 6.0 ± 0.0 | 6.0 ± 0.0 | ||
Reflexes absent and abnormal movements | 2.4 ± 0.24 | 2.0 ± 0.0 | ||
Total points | 13.6 ± 0.4 | 13.8 ± 0.2 | 0.671 | |
24 h | Motor tests | 4.0 ± 0.2 | 3.6 ± 0.24 | |
Sensory tests | 1.0 ± 0.0 | 1.2 ± 0.2 | ||
Beam balance tests | 5.8 ± 0.2 | 6.0 ± 0.0 | ||
Reflexes absent and abnormal movements | 1.0 ± 0.32 | 1.2 ± 0.2 | ||
Total points | 11.6 ± 0.24 | 12 ± 0.32 | 0.348 | |
48 h | Motor tests | 3.4 ± 0.24 | 3.0 ± 0.0 | |
Sensory tests | 1.2 ± 0.2 | 1.0 ± 0.0 | ||
Beam balance tests | 5.4 ± 0.24 | 5.4 ± 0.4 | ||
Reflexes absent and abnormal movements | 0.8 ± 0.2 | 1.2 ± 0.2 | ||
Total points | 10.8 ± 0.2 | 10.6 ± 0.4 | 0.671 | |
72 h | Motor tests | 3.0 ± 0.32 | 2.2 ± 0.37 | |
Sensory tests | 1.0 ± 0.32 | 0.6 ± 2.4 | ||
Beam balance tests | 5.6 ± 0.24 | 3.8 ± 0.49 | ||
Reflexes absent and abnormal movements | 1.0 ± 0.0 | 1.2 ± 0.2 | ||
Total points | 10.6 ± 0.4 | 7.8 ± 0.73 | 0.015 | |
7 days | Motor tests | 2.2 ± 0.37 | 1.0 ± 0.0 | |
Sensory tests | 0.8 ± 0.2 | 0.0 ± 0.0 | ||
Beam balance tests | 3.8 ± 0.58 | 1.2 ± 0.37 | ||
Reflexes absent and abnormal movements | 1.0 ± 0.0 | 0.6 ± 0.24 | ||
Total points | 7.8 ± 0.86 | 2.8 ± 0.58 | 0.002 |
Disease Models | Species | TRPM7 Inhibitors | Divalent Ions | Immunohistochemistry | Neurological Assessment | Reference |
---|---|---|---|---|---|---|
TBI | Rats | Carvacrol, 2-APB | Zn2+↓ | TRPM7 expression↓ Degenerating neurons↓ Dendritic injury↓ Oxidative/Nitrosative stress↓ Glutathione depletion↓ M1 microglial activation↓ Neuronal death↓ | Neurological dysfunction↓ | |
Stroke | Rats | Carvacrol, | Zn2+↓ | TRPM7 expression↓ Degenerating neurons↓ Dendritic injury↓ Oxidative stress↓ Microglial activation ↓ | N/A | [35] |
Epilepsy | Rats | Carvacrol, 2-APB | Zn2+↓ | TRPM7 expression↓ Degenerating neurons↓ Dendritic injury↓ Oxidative stress↓ M1 microglial activation↓ BBB disruption↓ Apoptosis↓ Neuronal death↓ | N/A | [36] |
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Lee, M.; Lee, S.H.; Choi, S.; Choi, B.Y.; Suh, S.W. Carvacrol Inhibits Expression of Transient Receptor Potential Melastatin 7 Channels and Alleviates Zinc Neurotoxicity Induced by Traumatic Brain Injury. Int. J. Mol. Sci. 2022, 23, 13840. https://doi.org/10.3390/ijms232213840
Lee M, Lee SH, Choi S, Choi BY, Suh SW. Carvacrol Inhibits Expression of Transient Receptor Potential Melastatin 7 Channels and Alleviates Zinc Neurotoxicity Induced by Traumatic Brain Injury. International Journal of Molecular Sciences. 2022; 23(22):13840. https://doi.org/10.3390/ijms232213840
Chicago/Turabian StyleLee, Minwoo, Song Hee Lee, Seunghyuk Choi, Bo Young Choi, and Sang Won Suh. 2022. "Carvacrol Inhibits Expression of Transient Receptor Potential Melastatin 7 Channels and Alleviates Zinc Neurotoxicity Induced by Traumatic Brain Injury" International Journal of Molecular Sciences 23, no. 22: 13840. https://doi.org/10.3390/ijms232213840