Fumagillin Attenuates Spinal Angiogenesis, Neuroinflammation, and Pain in Neuropathic Rats after Chronic Constriction Injury
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animal Preparation
2.2. Induction of Peripheral Neuropathy by CCI of the Sciatic Nerve
2.3. Construction and Implantation of i.t. Catheter and i.t. Drug Injection
2.4. Nociceptive Behavioral Assessment
2.4.1. Plantar Test for Thermal Stimulation
2.4.2. Von Frey Filament Test
2.4.3. Hot-Water Immersion Test
2.4.4. Narrow-Beam Walking Test
2.4.5. Weight Bearing Test
2.5. Western Blotting
2.6. Immunohistochemical Assay
2.7. Measurement of Cytokine Concentrations in the Spinal Cord
2.8. Drug Preparation
2.9. Statistical Analysis
3. Results
3.1. Animals
3.2. Time-Dependent Changes of Spinal VEGF Protein Levels in CCI Rats
3.3. CCI Upregulates CD31 and vWF Protein Levels in the Spinal Cord in a Similar Time-Dependent Manner
3.4. Neuroinflammation Enhances Pro-inflammatory Cytokine Release in the Ipsilateral Lumbar Spinal Cord after CCI
3.5. Intrathecal Administration of Fumagillin and Anti-VEGF-A Monoclonal Antibodies Attenuates CCI-Induced Neuropathic Pain
3.6. Intrathecal Fumagillin Attenuates CCI-Induced Angiogenesis in the Lumbar Spinal Cord
3.7. Fumagillin Differentially Modulates CCI-Induced Spinal Cytokine Production
3.8. Fumagillin Intrathecal Administration Attenuates CCI-Induced Astrocyte Activation in the Ipsilateral Lumbar Spinal Cord
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Wen, Z.-H.; Huang, S.-Y.; Kuo, H.-M.; Chen, C.-T.; Chen, N.-F.; Chen, W.-F.; Tsui, K.-H.; Liu, H.-T.; Sung, C.-S. Fumagillin Attenuates Spinal Angiogenesis, Neuroinflammation, and Pain in Neuropathic Rats after Chronic Constriction Injury. Biomedicines 2021, 9, 1187. https://doi.org/10.3390/biomedicines9091187
Wen Z-H, Huang S-Y, Kuo H-M, Chen C-T, Chen N-F, Chen W-F, Tsui K-H, Liu H-T, Sung C-S. Fumagillin Attenuates Spinal Angiogenesis, Neuroinflammation, and Pain in Neuropathic Rats after Chronic Constriction Injury. Biomedicines. 2021; 9(9):1187. https://doi.org/10.3390/biomedicines9091187
Chicago/Turabian StyleWen, Zhi-Hong, Shi-Ying Huang, Hsiao-Mei Kuo, Chao-Ting Chen, Nan-Fu Chen, Wu-Fu Chen, Kuan-Hao Tsui, Hsin-Tzu Liu, and Chun-Sung Sung. 2021. "Fumagillin Attenuates Spinal Angiogenesis, Neuroinflammation, and Pain in Neuropathic Rats after Chronic Constriction Injury" Biomedicines 9, no. 9: 1187. https://doi.org/10.3390/biomedicines9091187