Tauroursodeoxycholic Acid Reduces Neuroinflammation but Does Not Support Long Term Functional Recovery of Rats with Spinal Cord Injury
The bile acid tauroursodeoxycholic acid (TUDCA) reduces cell death under oxidative stress and inflammation. Implants of bone marrow-derived stromal cells (bmSC) are currently under investigation in clinical trials of spinal cord injury (SCI). Since cell death of injected bmSC limits the efficacy of...
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MDPI AG
2022-06-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/7/1501 |
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| author | Siyu Wu Concepción García-Rama Lorenzo Romero-Ramírez Johannes P. J. M. de Munter Erik Ch. Wolters Boris W. Kramer Jörg Mey |
| author_facet | Siyu Wu Concepción García-Rama Lorenzo Romero-Ramírez Johannes P. J. M. de Munter Erik Ch. Wolters Boris W. Kramer Jörg Mey |
| author_sort | Siyu Wu |
| collection | DOAJ |
| description | The bile acid tauroursodeoxycholic acid (TUDCA) reduces cell death under oxidative stress and inflammation. Implants of bone marrow-derived stromal cells (bmSC) are currently under investigation in clinical trials of spinal cord injury (SCI). Since cell death of injected bmSC limits the efficacy of this treatment, the cytoprotective effect of TUDCA may enhance its benefit. We therefore studied the therapeutic effect of TUDCA and its use as a combinatorial treatment with human bmSC in a rat model of SCI. A spinal cord contusion injury was induced at thoracic level T9. Treatment consisted of i.p. injections of TUDCA alone or in combination with one injection of human bmSC into the <i>cisterna magna.</i> The recovery of motor functions was assessed during a surveillance period of six weeks. Biochemical and histological analysis of spinal cord tissue confirmed the anti-inflammatory activity of TUDCA. Treatment improved the recovery of autonomic bladder control and had a positive effect on motor functions in the subacute phase, however, benefits were only transient, such that no significant differences between vehicle and TUDCA-treated animals were observed 1–6 weeks after the lesion. Combinatorial treatment with TUDCA and bmSC failed to have an additional effect compared to treatment with bmSC only. Our data do not support the use of TUDCA as a treatment of SCI. |
| first_indexed | 2024-03-09T10:21:56Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T10:21:56Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-16c44f35ff634158ac247e1c008857c92023-12-01T21:55:06ZengMDPI AGBiomedicines2227-90592022-06-01107150110.3390/biomedicines10071501Tauroursodeoxycholic Acid Reduces Neuroinflammation but Does Not Support Long Term Functional Recovery of Rats with Spinal Cord InjurySiyu Wu0Concepción García-Rama1Lorenzo Romero-Ramírez2Johannes P. J. M. de Munter3Erik Ch. Wolters4Boris W. Kramer5Jörg Mey6Hospital Nacional de Parapléjicos, 45071 Toledo, SpainHospital Nacional de Parapléjicos, 45071 Toledo, SpainHospital Nacional de Parapléjicos, 45071 Toledo, SpainNeuroplast BV, 6167 RD Geleen, The NetherlandsNeuroplast BV, 6167 RD Geleen, The NetherlandsSchool of Mental Health and Neuroscience and EURON Graduate School of Neuroscience, Maastricht University, 6229 ER Maastricht, The NetherlandsHospital Nacional de Parapléjicos, 45071 Toledo, SpainThe bile acid tauroursodeoxycholic acid (TUDCA) reduces cell death under oxidative stress and inflammation. Implants of bone marrow-derived stromal cells (bmSC) are currently under investigation in clinical trials of spinal cord injury (SCI). Since cell death of injected bmSC limits the efficacy of this treatment, the cytoprotective effect of TUDCA may enhance its benefit. We therefore studied the therapeutic effect of TUDCA and its use as a combinatorial treatment with human bmSC in a rat model of SCI. A spinal cord contusion injury was induced at thoracic level T9. Treatment consisted of i.p. injections of TUDCA alone or in combination with one injection of human bmSC into the <i>cisterna magna.</i> The recovery of motor functions was assessed during a surveillance period of six weeks. Biochemical and histological analysis of spinal cord tissue confirmed the anti-inflammatory activity of TUDCA. Treatment improved the recovery of autonomic bladder control and had a positive effect on motor functions in the subacute phase, however, benefits were only transient, such that no significant differences between vehicle and TUDCA-treated animals were observed 1–6 weeks after the lesion. Combinatorial treatment with TUDCA and bmSC failed to have an additional effect compared to treatment with bmSC only. Our data do not support the use of TUDCA as a treatment of SCI.https://www.mdpi.com/2227-9059/10/7/1501bile acidspinal cord injurybone marrow-derived stromal cellsratneuroinflammation |
| spellingShingle | Siyu Wu Concepción García-Rama Lorenzo Romero-Ramírez Johannes P. J. M. de Munter Erik Ch. Wolters Boris W. Kramer Jörg Mey Tauroursodeoxycholic Acid Reduces Neuroinflammation but Does Not Support Long Term Functional Recovery of Rats with Spinal Cord Injury Biomedicines bile acid spinal cord injury bone marrow-derived stromal cells rat neuroinflammation |
| title | Tauroursodeoxycholic Acid Reduces Neuroinflammation but Does Not Support Long Term Functional Recovery of Rats with Spinal Cord Injury |
| title_full | Tauroursodeoxycholic Acid Reduces Neuroinflammation but Does Not Support Long Term Functional Recovery of Rats with Spinal Cord Injury |
| title_fullStr | Tauroursodeoxycholic Acid Reduces Neuroinflammation but Does Not Support Long Term Functional Recovery of Rats with Spinal Cord Injury |
| title_full_unstemmed | Tauroursodeoxycholic Acid Reduces Neuroinflammation but Does Not Support Long Term Functional Recovery of Rats with Spinal Cord Injury |
| title_short | Tauroursodeoxycholic Acid Reduces Neuroinflammation but Does Not Support Long Term Functional Recovery of Rats with Spinal Cord Injury |
| title_sort | tauroursodeoxycholic acid reduces neuroinflammation but does not support long term functional recovery of rats with spinal cord injury |
| topic | bile acid spinal cord injury bone marrow-derived stromal cells rat neuroinflammation |
| url | https://www.mdpi.com/2227-9059/10/7/1501 |
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