David Gergely, Motovylyak Alice, Schlegel Felix, Kovacs Zsofia, Kündig Christian, Filous Angela R, Schwab Jan M, Budde Matthew D, Klohs Jan, Freund Patrick
Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland.
Department of Biomedical Engineering, Marquette University and Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Neurotrauma Rep. 2025 Jun 5;6(1):443-464. doi: 10.1089/neur.2025.0011. eCollection 2025.
In acute human spinal cord injury (SCI), magnetic resonance imaging (MRI) reveals progressive neuroanatomical changes at the lesion site and in remote regions. Here, we aimed to elucidate the structural underpinnings of these neuroanatomical changes and to characterize their spatiotemporal distribution in a rat contusion SCI model, using both histology and MRI. First, rats subjected to a thoracic contusion SCI (T8) and sham-operated rats were sacrificed at 56 days post-injury (dpi), and SMI-32 immunohistochemistry was used to assess remote axonal degeneration at cervical segments C2-C5. Second, to evaluate the effect of severity and time since injury on axonal degeneration, rats of varying injury severity were sacrificed at 2, 30, and 90 dpi, respectively, followed by SMI-32 immunohistochemistry. Third, structural MRI and diffusion tensor imaging were performed rostral to the injury site (C3-T6) at 90 dpi. Histological evidence of axonal degeneration emerged as early as 2 dpi rostral to the injury site, persisting at 90 dpi. Severity-dependent degeneration occurred within the fasciculus gracilis and the periphery of the medio- and ventrolateral columns. Corresponding MRI changes, including lower fractional anisotropy in these regions and smaller gray matter area, were detected. In contrast, the dorsal corticospinal tract exhibited lower fractional anisotropy without clear histological abnormalities, potentially due to atrophy-related mislocalization. This highlights the value of correlative, multimodal approaches and the need for further methodological refinement. The number of SMI-32+ axonal profiles correlated negatively, while gray matter area and fractional anisotropy correlated positively with locomotion assessed by Basso, Beattie, and Bresnahan scores. This study demonstrates in independent experiments that neuroanatomical MRI changes observed after SCI, occurring remote from the injury site, are linked to axonal degeneration. Experimental SCI offers translational insights into underlying mechanisms and potential avenues for neuroprotective or rehabilitative approaches.
在急性人类脊髓损伤（SCI）中，磁共振成像（MRI）显示损伤部位及远处区域存在渐进性神经解剖学变化。在此，我们旨在利用组织学和MRI阐明这些神经解剖学变化的结构基础，并在大鼠挫伤性SCI模型中描述其时空分布。首先，在损伤后56天（dpi）处死遭受胸段挫伤性SCI（T8）的大鼠和假手术大鼠，采用SMI-32免疫组织化学法评估颈段C2-Cs的远处轴突退变情况。其次，为评估损伤严重程度和损伤后时间对轴突退变的影响，分别在2、30和90 dpi处死不同损伤严重程度的大鼠，随后进行SMI-32免疫组织化学检测。第三，在90 dpi时对损伤部位（C3-T6）上方进行结构MRI和扩散张量成像。早在损伤部位上方2 dpi就出现了轴突退变的组织学证据，并持续至90 dpi。严重程度依赖性退变发生在薄束以及中间和腹外侧柱的周边。检测到相应的MRI变化，包括这些区域的分数各向异性降低和灰质面积减小。相比之下，皮质脊髓背束表现出较低的分数各向异性，但无明显的组织学异常，这可能是由于萎缩相关的定位错误所致。这凸显了相关多模态方法的价值以及进一步完善方法学的必要性。SMI-32+轴突轮廓数量呈负相关，而灰质面积和分数各向异性与通过Basso、Beattie和Bresnahan评分评估的运动能力呈正相关。本研究在独立实验中表明，SCI后观察到的远离损伤部位的神经解剖学MRI变化与轴突退变有关。实验性SCI为潜在机制以及神经保护或康复方法的潜在途径提供了转化性见解。
