Stevens Andrew R, Hadis Mohammed, Alldrit Hannah, Milward Michael R, Di Pietro Valentina, Gendoo Deena M A, Belli Antonio, Palin William, Davies David J, Ahmed Zubair
Neuroscience and Ophthalmology, Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham, Birmingham, B15 2TH, UK.
Sci Rep. 2025 Jan 25;15(1):3193. doi: 10.1038/s41598-025-87300-4.
Spinal cord injury (SCI) is a significant cause of lifelong disability, with no available disease-modifying treatments to promote neuroprotection and axon regeneration after injury. Photobiomodulation (PBM) is a promising therapy which has proven effective at restoring lost function after SCI in pre-clinical models. However, the precise mechanism of action is yet to be determined. Here, we used an in-vivo model of SCI in adult rats that received daily PBM (660 nm, 24 mW/cm, 1 min) and at three days post-injury, the injured spinal cord segment was harvested and subjected to whole transcriptome sequencing and subsequent pathway analysis (generally applicable gene-set enrichment (GAGE)). Pathway analysis demonstrated 1275 differentially expressed genes (DEGs) after PBM treatment, of which 397 were upregulated and 878 were downregulated. Key pathways were significantly enriched, including 8.6-fold enrichment of "neuron projection morphogenesis" (adjusted p = 8.10 × 10), with upregulation of Notch3, Slit1/Robo2 and Sema3g pathways. Ribosomal and oxidative phosphorylation pathways and NADH dehydrogenase were downregulated, and there was upregulation of ATP-dependent activity, cAMP and calcium signalling pathways. Key genes in apoptotic pathways were downregulated, as were S100 and cyclo-oxygenase components. Together, our study supports the favourable effects of PBM in promoting neuroregeneration and suppressing apoptosis after neurological injury. Further findings from pathway analysis suggest that downregulation of metabolism-associated pathways is a mechanism by which acute post-injury mitochondrial dysfunction may be averted by PBM therapy.
脊髓损伤（SCI）是导致终身残疾的一个重要原因，目前尚无可用的疾病改善治疗方法来促进损伤后的神经保护和轴突再生。光生物调节（PBM）是一种很有前景的疗法，在临床前模型中已被证明对脊髓损伤后恢复丧失的功能有效。然而，其确切的作用机制尚未确定。在此，我们使用成年大鼠的脊髓损伤体内模型，对其进行每日一次的PBM治疗（660纳米，24毫瓦/平方厘米，1分钟），在损伤后三天，采集损伤的脊髓节段并进行全转录组测序及后续的通路分析（一般适用基因集富集分析（GAGE））。通路分析显示，PBM治疗后有1275个差异表达基因（DEG），其中397个上调，878个下调。关键通路显著富集，包括“神经元投射形态发生”富集了8.6倍（校正p = 8.10×10），Notch3、Slit1/Robo2和Sema3g通路上调。核糖体和氧化磷酸化通路以及NADH脱氢酶下调，而ATP依赖性活性、cAMP和钙信号通路上调。凋亡通路中的关键基因下调，S100和环氧化酶成分也下调。总之，我们的研究支持了PBM在促进神经再生和抑制神经损伤后细胞凋亡方面的有利作用。通路分析的进一步结果表明，与代谢相关通路的下调是PBM疗法可能避免损伤后急性线粒体功能障碍的一种机制。
