Department of Neurosurgery, University Hospital Heidelberg, University of Heidelberg, INF 400, 69120 Heidelberg, Germany.
Department of Neuroanatomy, Institute for Anatomy and Cell Biology, University of Heidelberg, INF 307, 69120 Heidelberg, Germany.
Int J Mol Sci. 2021 Dec 3;22(23):13106. doi: 10.3390/ijms222313106.
Cervical spinal cord injury (SCI) remains a devastating event without adequate treatment options despite decades of research. In this context, the usefulness of common preclinical SCI models has been criticized. We, therefore, aimed to use a clinically relevant animal model of severe cervical SCI to assess the long-term effects of neural precursor cell (NPC) transplantation on secondary injury processes and functional recovery. To this end, we performed a clip contusion-compression injury at the C6 level in 40 female Wistar rats and a sham surgery in 10 female Wistar rats. NPCs, isolated from the subventricular zone of green fluorescent protein (GFP) expressing transgenic rat embryos, were transplanted ten days after the injury. Functional recovery was assessed weekly, and FluoroGold (FG) retrograde fiber-labeling, as well as manganese-enhanced magnetic resonance imaging (MEMRI), were performed prior to the sacrifice of the animals eight weeks after SCI. After cryosectioning of the spinal cords, immunofluorescence staining was conducted. Results were compared between the treatment groups (NPC, Vehicle, Sham) and statistically analyzed ( < 0.05 was considered significant). Despite the severity of the injury, leading to substantial morbidity and mortality during the experiment, long-term survival of the engrafted NPCs with a predominant differentiation into oligodendrocytes could be observed after eight weeks. While myelination of the injured spinal cord was not significantly improved, NPC treated animals showed a significant increase of intact perilesional motor neurons and preserved spinal tracts compared to untreated Vehicle animals. These findings were associated with enhanced preservation of intact spinal cord tissue. However, reactive astrogliosis and inflammation where not significantly reduced by the NPC-treatment. While differences in the Basso-Beattie-Bresnahan (BBB) score and the Gridwalk test remained insignificant, animals in the NPC group performed significantly better in the more objective CatWalk XT gait analysis, suggesting some beneficial effects of the engrafted NPCs on the functional recovery after severe cervical SCI.
颈椎脊髓损伤（SCI）仍然是一种毁灭性的疾病，尽管经过数十年的研究，但仍缺乏有效的治疗方法。在这种情况下，常见的 SCI 临床前模型的有效性受到了批评。因此，我们旨在使用一种与临床相关的严重颈椎 SCI 动物模型来评估神经前体细胞（NPC）移植对继发性损伤过程和功能恢复的长期影响。为此，我们在 40 只雌性 Wistar 大鼠中进行了 C6 水平的夹挫伤，在 10 只雌性 Wistar 大鼠中进行了假手术。NPC 是从 GFP 表达转基因大鼠胚胎的侧脑室下区分离出来的，在损伤后 10 天进行移植。每周评估功能恢复情况，并在 SCI 后 8 周处死动物前进行 FluoroGold（FG）逆行纤维标记和锰增强磁共振成像（MEMRI）。对脊髓进行冷冻切片后，进行免疫荧光染色。将治疗组（NPC、Vehicle、Sham）的结果进行比较，并进行统计学分析（<0.05 被认为具有统计学意义）。尽管损伤严重，导致实验过程中发病率和死亡率较高，但在 8 周后仍能观察到移植 NPC 的长期存活，且主要分化为少突胶质细胞。尽管损伤脊髓的髓鞘形成没有显著改善，但与未治疗的 Vehicle 动物相比，NPC 治疗动物的受损运动神经元和保留的脊髓束明显增多。这些发现与完整脊髓组织的更好保存有关。然而，NPC 治疗并未显著减少反应性星形胶质细胞增生和炎症。尽管 Basso-Beattie-Bresnahan（BBB）评分和网格行走测试的差异不显著，但 NPC 组动物在更客观的 CatWalk XT 步态分析中表现更好，提示移植 NPC 对严重颈椎 SCI 后的功能恢复有一些有益影响。
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