Schading-Sassenhausen Simon, Lebret Anna, Şimşek Kadir, Gut Pauline, Imhof Sabrina, Zörner Björn, Kreis Roland, Freund Patrick, Seif Maryam
Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland.
Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University, Cardiff, UK.
J Neurosci Res. 2025 Jul;103(7):e70071. doi: 10.1002/jnr.70071.
Spinal cord injury (SCI) disrupts spinal tracts and neuronal pathways, including those in the primary motor cortex (M1) and the lumbar cord enlargement (LCE) involved in motor control. This study sought to determine whether metabolite concentrations deviate between SCI and healthy controls (HC) in M1 and LCE using proton magnetic resonance spectroscopy (H-MRS) and structural MRI, and if these correlate with clinical impairment. Sixteen chronic SCI (mean age: 54.7 ± 14.8y) and 19 HCs (mean age: 53.2 ± 18.8y) underwent H-MRS to quantify metabolites along with T- and T*-weighted MRI to assess tissue structural changes. Associations between metabolic and structural changes and clinical impairment were also assessed. Patients showed significant atrophy in both white matter of the LCE (HC: 37.7 ± 4.7 mm, SCI: 33.9 ± 3.7 mm, Δ = -10.1%, p = 0.015) and gray matter (HC: 20.9 ± 2.1 mm, SCI: 19.4 ± 1.5 mm, Δ = -7.2%, p = 0.022). Total N-acetylaspartate (tNAA) with respect to total creatine (tCr) was reduced in M1 of SCI (HC: 1.94 ± 0.21, SCI: 1.77 ± 0.14, ∆ = -8.8%, p = 0.006) and in the LCE (HC: 2.48 ± 0.76, SCI: 1.81 ± 0.80, ∆ = -27.0%, p = 0.02). In conclusion, reduced tNAA/tCr in both the atrophied LCE and M1 suggests widespread neuronal changes including cell atrophy and/or cell loss after injury. These findings provide in vivo evidence for retrograde and trans-synaptic neurodegeneration, which may underline the atrophy observed in the motor system in SCI. Ultimately, this highlights the potential for metabolic and structural biomarkers to improve the monitoring of subtle neurodegeneration following SCI and to enhance future regenerative treatment strategies.
脊髓损伤（SCI）会破坏脊髓传导束和神经通路，包括初级运动皮层（M1）和参与运动控制的腰髓膨大（LCE）中的神经通路。本研究旨在使用质子磁共振波谱（H-MRS）和结构磁共振成像（MRI）来确定SCI患者与健康对照者（HC）在M1和LCE中的代谢物浓度是否存在差异，以及这些差异是否与临床损伤相关。16名慢性SCI患者（平均年龄：54.7±14.8岁）和19名HC（平均年龄：53.2±18.8岁）接受了H-MRS以定量代谢物，并接受了T加权和T*加权MRI以评估组织结构变化。还评估了代谢和结构变化与临床损伤之间的关联。患者的LCE白质（HC：37.7±4.7mm，SCI：33.9±3.7mm，Δ=-10.1%，p=0.015）和灰质（HC：20.9±2.1mm，SCI：19.4±1.5mm，Δ=-7.2%；p=0.022）均出现明显萎缩。SCI患者M1中总N-乙酰天门冬氨酸（tNAA）与总肌酸（tCr）的比值降低（HC：1.94±0.21，SCI：1.77±0.14，∆=-8.8%，p=0.006），LCE中也降低（HC：2.48±0.76，SCI：1.81±0.80，∆=-27.0%，p=0.02）。总之，萎缩的LCE和M1中tNAA/tCr降低表明损伤后存在广泛的神经元变化，包括细胞萎缩和/或细胞丢失。这些发现为逆行性和跨突触神经变性提供了体内证据，这可能是SCI运动系统中观察到的萎缩的基础。最终，这突出了代谢和结构生物标志物在改善SCI后细微神经变性监测以及加强未来再生治疗策略方面的潜力。
