1 INSERM U1198, University of Montpellier, Montpellier, France.
2 INSERM U1051, University of Montpellier, Montpellier, France.
J Neurotrauma. 2018 Dec 15;35(24):2924-2940. doi: 10.1089/neu.2017.5613. Epub 2018 Aug 10.
Spinal cord injuries (SCI) are disastrous neuropathologies causing permanent disabilities. The availability of different strains of mice is valuable for studying the pathophysiological mechanisms involved in SCI. However, strain differences have a profound effect on spontaneous functional recovery after SCI. CX3CR1 and Aldh1l1-EGFP mice that express green fluorescent protein in microglia/monocytes and astrocytes, respectively, are particularly useful to study glial reactivity. Whereas CX3CR1 mice have C57BL/6 background, Aldh1l1-EGFP are in Swiss Webster background. We first assessed spontaneous functional recovery in CX3CR1 and Aldh1l1-EGFP mice over 6 weeks after lateral spinal cord hemisection. Second, we carried out a longitudinal follow-up of lesion evolution using in vivo T2-weighted magnetic resonance imaging (MRI). Finally, we performed in-depth analysis of the spinal cord tissue using ex vivo T2-weighted MRI as well as detailed histology. We demonstrate that CX3CR1 mice have improved functional recovery and reduced anxiety after SCI compared with Aldh1l1-EGFP mice. We also found a strong correlation between in vivo MRI, ex vivo MRI, and histological analyses of the injured spinal cord in both strain of mice. All three modalities revealed no difference in lesion extension and volume between the two strains of mice. Importantly, histopathological analysis identified decreased gliosis and increased serotonergic axons in CX3CR1 compared with Aldh1l1-EGFP mice following SCI. These results thus suggest that the strain-dependent improved functional recovery after SCI may be linked with reduced gliosis and increased serotonergic innervation.
脊髓损伤（SCI）是一种灾难性的神经病理学疾病，会导致永久性残疾。不同品系的小鼠的可用性对于研究 SCI 涉及的病理生理机制非常有价值。然而，品系差异对 SCI 后的自发功能恢复有深远的影响。分别在小胶质细胞/单核细胞和星形胶质细胞中表达绿色荧光蛋白的 CX3CR1 和 Aldh1l1-EGFP 小鼠对于研究神经胶质反应特别有用。虽然 CX3CR1 小鼠具有 C57BL/6 背景，但 Aldh1l1-EGFP 则具有瑞士 Webster 背景。我们首先评估了 CX3CR1 和 Aldh1l1-EGFP 小鼠在侧脊髓半切后 6 周内的自发功能恢复情况。其次，我们使用体内 T2 加权磁共振成像（MRI）进行了病变演变的纵向随访。最后，我们使用离体 T2 加权 MRI 以及详细的组织学进行了脊髓组织的深入分析。我们证明与 Aldh1l1-EGFP 小鼠相比，CX3CR1 小鼠在 SCI 后具有更好的功能恢复和更低的焦虑水平。我们还发现，在两种品系的小鼠中，体内 MRI、离体 MRI 和损伤脊髓的组织学分析之间存在很强的相关性。所有三种方法均未发现两种品系小鼠之间的病变扩展和体积存在差异。重要的是，组织病理学分析表明，与 Aldh1l1-EGFP 小鼠相比，CX3CR1 小鼠在 SCI 后神经胶质增生减少，5-羟色胺能轴突增加。因此，这些结果表明，SCI 后功能恢复的品系依赖性改善可能与神经胶质增生减少和 5-羟色胺能神经支配增加有关。
