Effect of valproic acid combined with transplantation of olfactory ensheathing cells modified by neurotrophic 3 gene on nerve protection and repair after traumatic brain injury

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM Neuropeptides Pub Date : 2023-10-26 DOI:10.1016/j.npep.2023.102389

Haiming Li , Zhijie Yin , Shuangzhu Yue , Yunying An , Xiaoyin Wang , Shifang Zhou , Lei Meng , Baozhe Jin

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Abstract

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.

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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颅脑损伤后神经保护和修复的影响。

背景：创伤性脑损伤（TBI）经常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；神经营养因子3基因（NT-3）可以维持神经元的存活，嗅觉鞘细胞（OECs）可以促进神经轴突的生长。本研究旨在评价VPA联合NT-3修饰OECs（NT-3-OECs）对大鼠TBI后神经功能的恢复作用。苏木精-伊红（HE）染色、p75神经生长因子受体（p75）、胶质原纤维酸性蛋白（GFAP）和神经丝蛋白（NF）染色以及嗜银染色用于观察建模后28天的脑组织形态。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。电镜观察损伤区突触和线粒体的变化。结果：NT-3-OECs移植可提高脑组织中NT-3的含量，NT-3-OECs可存活28天以上。TBI-VPA-NT-3-OECs组在细胞移植后28天的NSS评分显著低于其他模型治疗组（P结论：NT-3-OECs具有良好的生物学功能，VPA联合NT-3-OEC移植可有效改善TBI大鼠的预后。

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文献相关原料

公司名称	产品信息	其他信息	采购帮参考价格
上海源叶	Valproic acid		￥8.00~￥10985.00

来源期刊

Neuropeptides 医学-内分泌学与代谢

CiteScore

5.40

自引率

6.90%

发文量

审稿时长

>12 weeks

期刊介绍： The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.