Delayed atorvastatin delivery promotes recovery after experimental spinal cord injury
Spinal cord injury (SCI) significantly alters gene expression, potentially impeding functional recovery. This study investigated the effects of atorvastatin, a widely prescribed cholesterol-lowering drug, on gene expression and functional recovery in a chronic murine SCI model. Female C57BL/6J mice...
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Elsevier
2025-03-01
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| Series: | Neurotherapeutics |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878747924002046 |
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| author | Samuel C. Buchl Ha Neui Kim Benjamin Hur Whitney L. Simon Monica R. Langley Jaeyun Sung Isobel A. Scarisbrick |
| author_facet | Samuel C. Buchl Ha Neui Kim Benjamin Hur Whitney L. Simon Monica R. Langley Jaeyun Sung Isobel A. Scarisbrick |
| author_sort | Samuel C. Buchl |
| collection | DOAJ |
| description | Spinal cord injury (SCI) significantly alters gene expression, potentially impeding functional recovery. This study investigated the effects of atorvastatin, a widely prescribed cholesterol-lowering drug, on gene expression and functional recovery in a chronic murine SCI model. Female C57BL/6J mice underwent moderate 0.25 mm lateral compression SCI and received daily atorvastatin (10 mg/kg) or vehicle-only injections from two weeks post-injury for four weeks. Sensorimotor functions were assessed using the Basso Mouse Scale (BMS), its subscore, and the inclined plane test. RNA sequencing of spinal cord tissues identified robust transcriptomic changes from SCI and a smaller subset from atorvastatin treatment. Atorvastatin enhanced sensorimotor recovery within two weeks of treatment initiation, with effects persisting to the experimental endpoint. Pathway analysis showed atorvastatin enriched neural regeneration processes including Fatty Acid Transport, Axon Guidance, and the Endocannabinoid Developing Neuron Pathway; improved mitochondrial function via increased TCA Cycle II and reduced Mitochondrial Dysfunction; and decreased Inhibition of Matrix Metalloproteases. Key gene drivers included Fabp7, Unc5c, Rest, and Klf4. Together, these results indicate atorvastatin's potential in chronic SCI recovery, especially where already indicated for cardiovascular protection. |
| format | Article |
| id | doaj-art-c91b03a87c544da18edecd42853d3d2e |
| institution | OA Journals |
| issn | 1878-7479 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurotherapeutics |
| spelling | doaj-art-c91b03a87c544da18edecd42853d3d2e2025-08-20T02:18:00ZengElsevierNeurotherapeutics1878-74792025-03-01222e0051710.1016/j.neurot.2024.e00517Delayed atorvastatin delivery promotes recovery after experimental spinal cord injurySamuel C. Buchl0Ha Neui Kim1Benjamin Hur2Whitney L. Simon3Monica R. Langley4Jaeyun Sung5Isobel A. Scarisbrick6Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, USADepartment of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USAMicrobiomics Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA; Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USAMayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, USA; Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA; Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USADepartment of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA; Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USAMicrobiomics Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA; Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA; Division of Rheumatology, Department of Medicine, Mayo Clinic, Rochester, MN, USAMayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, USA; Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA; Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USA; Corresponding author.Spinal cord injury (SCI) significantly alters gene expression, potentially impeding functional recovery. This study investigated the effects of atorvastatin, a widely prescribed cholesterol-lowering drug, on gene expression and functional recovery in a chronic murine SCI model. Female C57BL/6J mice underwent moderate 0.25 mm lateral compression SCI and received daily atorvastatin (10 mg/kg) or vehicle-only injections from two weeks post-injury for four weeks. Sensorimotor functions were assessed using the Basso Mouse Scale (BMS), its subscore, and the inclined plane test. RNA sequencing of spinal cord tissues identified robust transcriptomic changes from SCI and a smaller subset from atorvastatin treatment. Atorvastatin enhanced sensorimotor recovery within two weeks of treatment initiation, with effects persisting to the experimental endpoint. Pathway analysis showed atorvastatin enriched neural regeneration processes including Fatty Acid Transport, Axon Guidance, and the Endocannabinoid Developing Neuron Pathway; improved mitochondrial function via increased TCA Cycle II and reduced Mitochondrial Dysfunction; and decreased Inhibition of Matrix Metalloproteases. Key gene drivers included Fabp7, Unc5c, Rest, and Klf4. Together, these results indicate atorvastatin's potential in chronic SCI recovery, especially where already indicated for cardiovascular protection.http://www.sciencedirect.com/science/article/pii/S1878747924002046Chronic spinal cord injuryLocomotor recoveryRNA sequencingSpinal cord transcriptomicsPathway analysis |
| spellingShingle | Samuel C. Buchl Ha Neui Kim Benjamin Hur Whitney L. Simon Monica R. Langley Jaeyun Sung Isobel A. Scarisbrick Delayed atorvastatin delivery promotes recovery after experimental spinal cord injury Neurotherapeutics Chronic spinal cord injury Locomotor recovery RNA sequencing Spinal cord transcriptomics Pathway analysis |
| title | Delayed atorvastatin delivery promotes recovery after experimental spinal cord injury |
| title_full | Delayed atorvastatin delivery promotes recovery after experimental spinal cord injury |
| title_fullStr | Delayed atorvastatin delivery promotes recovery after experimental spinal cord injury |
| title_full_unstemmed | Delayed atorvastatin delivery promotes recovery after experimental spinal cord injury |
| title_short | Delayed atorvastatin delivery promotes recovery after experimental spinal cord injury |
| title_sort | delayed atorvastatin delivery promotes recovery after experimental spinal cord injury |
| topic | Chronic spinal cord injury Locomotor recovery RNA sequencing Spinal cord transcriptomics Pathway analysis |
| url | http://www.sciencedirect.com/science/article/pii/S1878747924002046 |
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