Background

Traumatic brain injury (TBI) often leads to cognitive and neurological dysfunction. Valproic acid (VPA) has a neuroprotective effect in acute central nervous system diseases; the neurotrophin 3 gene (NT-3) can maintain the survival of neurons, and olfactory ensheathing cells (OECs) can promote the growth of nerve axons. This study aimed to evaluate the restorative effect of VPA combined with NT-3 modified OECs (NT-3-OECs) on neurological function after TBI.

Methods

The neurological severity score (NSS) of rats was evaluated on the 1st, 7th, 14th, and 28th day after TBI modeling and corresponding intervention. Hematoxylin-eosin (HE) staining, p75 nerve growth factor receptor (P75), glial fibrillary acidic protein (GFAP), and neurofilament protein (NF)staining, and argyrophilic staining were used to observe the morphology of brain tissue 28 days after modeling. Moreover, TdT-mediated dUTP Nick-End Labeling (TUNEL) was used to detect the apoptosis rate of neurons. The changes in synapses and mitochondria in the injured area were observed by electron microscope.

Results

NT-3-OECs transplantation can increase the content of NT-3 in brain tissue, and NT-3-OECs can survive for >28 days. The NSS score of the TBI-VPA-NT-3-OECs group 28 days after cell transplantation was significantly lower than that of the other model treatment groups (P < 0.05). The morphological structure of the brain tissue was more complete, and the neurofilament fibers were neatly arranged, achieving better results than those of the other groups. The apoptosis rate of nerve cells in the TBI-VPA-NT-3-OECs group was significantly lower than in the other treatment groups (P < 0.05). Furthermore, the number of synapses in the combined intervention group was significantly higher than in the other treatment groups, and the mitochondrial structure was more complete.

Conclusion

NT-3-OECs have good biological function, and VPA combined with NT-3-OECs transplantation can effectively improve the prognosis of TBI rats.

中文翻译：

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丙戊酸联合神经营养3基因修饰的嗅鞘细胞移植对脑外伤后神经保护与修复的影响

背景

创伤性脑损伤（TBI）通常会导致认知和神经功能障碍。丙戊酸（VPA）对急性中枢神经系统疾病具有神经保护作用；神经营养蛋白3基因（NT-3）可以维持神经元的存活，嗅鞘细胞（OEC）可以促进神经轴突的生长。本研究旨在评估VPA联合NT-3修饰的OECs（NT-3-OECs）对TBI后神经功能的恢复作用。

方法

在TBI造模及相应干预后第1、7、14、28天评估大鼠神经严重程度评分（NSS）。造模后28天采用苏木精-伊红（HE）染色、p75神经生长因子受体（P75）、胶质纤维酸性蛋白（GFAP）、神经丝蛋白（NF）染色、嗜银染色观察脑组织形态。此外，TdT介导的dUTP缺口末端标记（TUNEL）用于检测神经元的凋亡率。电镜观察损伤部位突触和线粒体的变化。

结果

NT-3-OECs移植可增加脑组织中NT-3的含量，NT-3-OECs可存活>28天。TBI-VPA-NT-3-OECs 组细胞移植后 28 d 的 NSS 评分显着低于其他模型治疗组（P  < 0.05）。脑组织形态结构更加完整，神经丝纤维排列整齐，取得了比其他组更好的结果。TBI-VPA-NT-3-OECs 组神经细胞凋亡率显着低于其他治疗组（P  < 0.05）。此外，联合干预组的突触数量显着高于其他治疗组，线粒体结构更完整。

结论

NT-3-OECs具有良好的生物学功能，VPA联合NT-3-OECs移植可有效改善TBI大鼠的预后。