Liu Le, Fang Liwei, Duan Boyang, Wang Yue, Cui Zhenzhen, Yang Li, Wu De
Department of Pediatrics, Pediatric Neurorehabilitation Center, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Department of Pediatrics, Maternal and Child Health Hospital, The Affiliated Hospital of Anhui Medical University, Hefei, China.
Front Pediatr. 2022 Jun 6;10:867410. doi: 10.3389/fped.2022.867410. eCollection 2022.
Cerebral palsy (CP) is a group of permanent, but not unchanging, disorders of movement and/or posture and motor function. Since the major brain injury associated with CP is white matter injury (WMI), especially, in preterm infants, we established a "multi-hit" rat model to mimic human WMI in symptomatology and at a histological level. In our WMI model, pups suffering from limb paresis, incoordination, and direction difficulties fit the performance of CP. Histologically, they present with fewer neural cells, inordinate fibers, and more inflammatory cell infiltration, compared to the control group. From the electron microscopy results, we spotted neuronal apoptosis, glial activation, and myelination delay. Besides, the abundant appearance of IBA1-labeled microglia also implied that microglia play a role during neuronal cell injury. After activation, microglia shift between the pro-inflammatory M1 type and the anti-inflammatory M2 type. The results showed that LPS/infection stimulated IBA1 + (marked activated microglia) expression, downregulated CD11c + (marked M1 phenotype), and upregulated Arg 1 + (marked M2 phenotype) protein expression. It indicated an M1 to M2 transition after multiple infections. In summary, we established a "multi-hit" WMI-induced CP rat model and demonstrated that the microglial activation correlates tightly with CP formation, which may become a potential target for future studies.
脑性瘫痪（CP）是一组永久性但并非一成不变的运动和/或姿势及运动功能障碍。由于与CP相关的主要脑损伤是白质损伤（WMI），尤其是在早产儿中，我们建立了一种“多重打击”大鼠模型，以在症状学和组织学水平上模拟人类WMI。在我们的WMI模型中，患有肢体轻瘫、不协调和方向困难的幼崽符合CP的表现。组织学上，与对照组相比，它们的神经细胞较少、纤维紊乱且炎症细胞浸润更多。从电子显微镜结果来看，我们发现了神经元凋亡、胶质细胞活化和髓鞘形成延迟。此外，IBA1标记的小胶质细胞大量出现也表明小胶质细胞在神经元细胞损伤过程中发挥作用。激活后，小胶质细胞在促炎M1型和抗炎M2型之间转变。结果显示，脂多糖/感染刺激了IBA1 +（标记活化的小胶质细胞）表达，下调了CD11c +（标记M1表型），并上调了Arg 1 +（标记M2表型）蛋白表达。这表明多次感染后发生了从M1到M2的转变。总之，我们建立了一种“多重打击”WMI诱导的CP大鼠模型，并证明小胶质细胞活化与CP形成密切相关，这可能成为未来研究的一个潜在靶点。
