Delayed atorvastatin delivery promotes recovery after experimental spinal cord injury

被引：0
作者：
Buchl, Samuel C. [1 ]
Kim, Ha Neui [2 ]
Hur, Benjamin [3 ,4 ]
Simon, Whitney L. [1 ,2 ,5 ]
Langley, Monica R. [2 ,5 ]
Sung, Jaeyun [3 ,4 ,6 ]
Scarisbrick, Isobel A. [1 ,2 ,5 ]
机构：
[1] Mayo Clin, Grad Sch Biomed Sci, Rochester, MN 55905 USA
[2] Mayo Clin, Dept Phys Med & Rehabil, Rochester, MN 55905 USA
[3] Mayo Clin, Ctr Individualized Med, Microbi Program, Rochester, MN USA
[4] Mayo Clin, Dept Quantitat Hlth Sci, Div Computat Biol, Rochester, MN USA
[5] Mayo Clin, Ctr Multiple Sclerosis & Autoimmune Neurol, Rochester, MN 55905 USA
[6] Mayo Clin, Dept Med, Div Rheumatol, Rochester, MN USA
来源：
NEUROTHERAPEUTICS | 2025年 / 22卷 / 02期
基金：
美国国家卫生研究院;
关键词：
Chronic spinal cord injury; Locomotor recovery; RNA sequencing; Spinal cord transcriptomics; Pathway analysis; BLOOD-BRAIN-BARRIER; FUNCTIONAL RECOVERY; DOWN-REGULATION; EXPRESSION; MODEL; CHOLESTEROL; DISEASE; UNC5C; RISK; SIMVASTATIN;
D O I：
10.1016/j.neurot.2024.e00517
中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
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.
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页数：13
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