切换至 "中华医学电子期刊资源库"
高级检索
中华神经创伤外科电子杂志

中华神经创伤外科电子杂志 ›› 2017, Vol. 03 ›› Issue (06) : 355 -359. doi: 10.3877/cma.j.issn.2095-9141.2017.06.008

所属专题： 文献；

基础研究

诱导型神经干细胞对颅脑创伤后免疫细胞的影响
高谋1, 徐如祥1,†(), 王海峰2, 许民辉1, 董勤1, 姚慧1, 张岩1, 杨阳1, 党圆圆1, 张洪钿1, 杨志军1   
  1. 1. 100700　北京，陆军总医院附属八一脑科医院
    2. 130021　长春，吉林大学第一医院神经创伤外科
  • 收稿日期:2017-10-26 出版日期:2017-12-15
  • 通信作者: 徐如祥
  • 基金资助:
    国家自然科学基金(81671189); 全军"十三五"军事医学创新工程项目(16CXZ001)

Effects of induced neural stem cells on immune cells following traumatic brain injury

Mou Gao1, Ruxiang Xu1,†(), Haifeng Wang2, Minhui Xu1, Qin Dong1, Hui Yao1, Yan Zhang1, Yang Yang1, Yuanyuan Dang1, Hongtian Zhang1, Zhijun Yang1   

  1. 1. Affiliated Bayi Brain Hospital, General Hospital of PLA Army, Beijing 100700, China
    2. Department of Neurotrauma, First Hospital of Jilin University, Changchun 130021, China
  • Received:2017-10-26 Published:2017-12-15
  • Corresponding author: Ruxiang Xu
  • About author:
    Corresponding author: Xu Ruxiang, Email:
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

高谋, 徐如祥, 王海峰, 许民辉, 董勤, 姚慧, 张岩, 杨阳, 党圆圆, 张洪钿, 杨志军. 诱导型神经干细胞对颅脑创伤后免疫细胞的影响[J]. 中华神经创伤外科电子杂志, 2017, 03(06): 355-359.

Mou Gao, Ruxiang Xu, Haifeng Wang, Minhui Xu, Qin Dong, Hui Yao, Yan Zhang, Yang Yang, Yuanyuan Dang, Hongtian Zhang, Zhijun Yang. Effects of induced neural stem cells on immune cells following traumatic brain injury[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2017, 03(06): 355-359.

目的

研究诱导型神经干细胞（iNSCs）移植对颅脑创伤（TBI）后小胶质细胞活化状态和反应性星形胶质细胞增生的影响。

方法

采用自由落体脑打击装置制备C57BL/6小鼠TBI模型，将1×106个iNSCs移植到TBI小鼠脑内，于移植后7 d处死动物，取材进行形态学研究。用双重免疫荧光染色，分别观察iNSCs移植对TBI小鼠脑内ED1和Iba1抗体双阳性的小胶质细胞、GFAP抗体阳性星形胶质细胞以及NeuN抗体阳性神经元的影响。

结果

TBI后小鼠脑内可见大量ED1和Iba1抗体双阳性的小胶质细胞和GFAP抗体阳性的星形胶质细胞，而iNSCs移植物明显减少了ED1和Iba1抗体双阳性的小胶质细胞和GFAP抗体阳性的星形胶质细胞的数量，并且明显减轻了NeuN抗体阳性的神经元的凋亡。

结论

iNSCs移植物在TBI小鼠脑内，可调控小胶质细胞活化状态，抑制反应性星形胶质细胞增生，有利于神经元存活。

关键词: 诱导型神经干细胞, 小胶质细胞, 星形胶质细胞, 颅脑创伤, 移植
Objective

To study the effects of grafted induced neural stem cells (iNSCs) on microglia activation states and reactive astrogliosis following traumatic brain injury (TBI).

Methods

TBI models were established using a standardized weight-drop device. At 12 h after TBI, a total of 1×106 iNSCs were transplanted into the brains of TBI mice. On day 7 after TBI, animals were sacrificed for morphological analysis. Double-labeling experiments were utilized to determine the effects of iNSC grafts on ED1-and Iba1-positive microglia, GFAP-positive astrocytes and NeuN-positive neurons in the brains of TBI mice.

Results

Following TBI, we observed dramatic increases in the numbers of ED1- and Iba1-positive microglia and GFAP-positive astrocytes in the brains of TBI mice. However, grafted iNSCs significantly suppressed the numbers of ED1- and Iba1-positive microglia and GFAP-positive astrocytes in the brains of TBI mice. Additionally, iNSC grafts substantially reduced the levels of apoptotic NeuN-positive neurons in the brains of TBI mice.

Conclusion

INSC grafts can modulate microglia activation states and inhibit reactive astrogliosis to promote neuronal survival post-TBI.

Key words: Induced neural stem cell, Microglia, Astrocyte, Traumatic brain injury, Transplantation
图1 诱导型神经干细胞移植物减少颅脑损伤小鼠脑内ED1和Iba1抗体双阳性的小胶质细胞数量（×400）
表1 颅脑损伤后7 d，各组小鼠脑内特异性抗体标记细胞的百分率（±s，%）
组别 只数 ED1和Iba1抗体双阳性的小胶质细胞 GFAP抗体阳性星形胶质细胞 NeuN抗体阳性神经元
sham组 6 1.40±0.33 11.24±1.63 58.71±4.07
iNSCs移植组 6 21.40±2.04a 21.95±1.94a 21.29±1.96a
PBS处理组 6 29.39±2.89ab 29.50±2.27ab 16.45±1.52ab
F值 ? 296.320 131.030 424.000
P值 ? 0.000 0.000 0.000
图2 诱导型神经干细胞移植物减少颅脑损伤小鼠脑内GFAP抗体阳性星形胶质细胞数量（×400）
[1]
Goldman SA. Stem and progenitor cell-based therapy of the central nervous system: hopes, hype, and wishful thinking[J]. Cell Stem Cell, 2016, 18(2): 174-188.
[2]
Yao H,Gao M,Ma J, et al. Transdifferentiation-induced neural stem cells promote recovery of middle cerebral artery stroke rats[J]. PloS One, 2015, 10(9): e0137211.
[3]
Gao M,Yao H,Dong Q, et al. Tumourigenicity and immunogenicity of induced neural stem cell grafts versus induced pluripotent stem cell grafts in syngeneic mouse brain[J]. Sci Rep, 2016, 6: 29955.
[4]
高谋,徐如祥,许民辉,等.诱导神经干细胞与诱导多能干细胞在同源宿主脑内的致瘤性及免疫原性研究[J].中华神经创伤外科电子杂志, 2016, 2(6): 350-354.
[5]
Kim HS,Kim J,Jo Y, et al. Direct lineage reprogramming of mouse fibroblasts to functional midbrain dopaminergic neuronal progenitors[J]. Stem Cell Res, 2014, 12(1): 60-68.
[6]
Kokaia Z,Martino G,Schwartz M, et al. Cross-talk between neural stem cells and immune cells: the key to better brain repair[J]. Nat Neurosci, 2012, 15(8): 1078-1087.
[7]
Gao M,Yao H,Dong Q, et al. Neurotrophy and immunomodulation of induced neural stem cell grafts in a mouse model of closed head injury[J]. Stem Cell Res, 2017, 23: 132-142.
[8]
高谋,徐如祥,杨志军,等.两种干细胞对颅脑创伤炎症反应调控作用的对比研究[J].第三军医大学学报, 2015, 37(17): 1697-1703.
[9]
Cartier N,Lewis CA,Zhang R, et al. The role of microglia in human disease: therapeutic tool or target[J]. ActaNeuropathol, 2014, 128(3): 363-380.
[10]
Amor S,Woodroofe MN. Innate and adaptive immune responses in neurodegeneration and repair[J]. Immunology, 2014, 141(3): 287-291.
[11]
Sofroniew MV. Astrocyte barriers to neurotoxic inflammation[J]. Nat Rev Neurosci, 2015, 16(5): 249-263.
[12]
Corps KN,Roth TL,McGavern DB. Inflammation and neuroprotection in traumatic brain injury[J]. JAMA Neurol, 2015, 72(3): 355-362.
[13]
Kumar A,Barrett JP,Alvarez-Croda DM, et al. NOX2 drives M1-like microglial/macrophage activation and neurodegeneration following experimental traumatic brain injury[J]. Brain BehavImmun, 2016, 58: 291-309.
[14]
Hernandez-Ontiveros DG,Tajiri N,Acosta S, et al. Microglia activation as a biomarker for traumatic brain injury[J]. Front Neurol, 2013, 4: 30.
[15]
Mouzon BC,Bachmeier C,Ferro A, et al. Chronic neuropathological and neurobehavioral changes in a repetitive mild traumatic brain injury model[J]. Ann Neurol, 2014, 75(2): 241-254.
[16]
Glushakova OY,Johnson D,Hayes RL. Delayed increases in microvascular pathology after experimental traumatic brain injury are associated with prolonged inflammation, blood-brain barrier disruption, and progressive white matter damage[J]. J Neurotrauma, 2014, 31(13): 1180-1193.
[17]
Mayo L,Trauger SA,Blain M, et al. Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation[J]. Nat Med, 2014, 20(10): 1147-1156.
[18]
Rothhammer V,Mascanfroni ID,Bunse L, et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor[J]. Nat Med, 2016, 22(6): 586-597.
[19]
Xanthos DN,Sandkuhler J. Neurogenic neuroinflammation: inflammatory CNS reactions in response to neuronal activity[J]. Nat Rev Neurosci, 2014, 15(1): 43-53.
[1] 谢迎东, 孙帼, 徐超丽, 杨斌, 孙晖, 戴云. 超声造影定量评价不同生存期移植肾血流灌注的临床价值[J]. 中华医学超声杂志（电子版）, 2023, 20(07): 749-754.
[2] 罗旺林, 杨传军, 许国星, 俞建国, 孙伟东, 颜文娟, 冯志. 开放性楔形胫骨高位截骨术不同植入材料的Meta分析[J]. 中华关节外科杂志(电子版), 2023, 17(06): 818-826.
[3] 刘林峰, 王增涛, 王云鹏, 钟硕, 郝丽文, 仇申强, 陈超. 足底内侧皮瓣联合甲骨皮瓣在手指V度缺损再造中的临床应用[J]. 中华损伤与修复杂志(电子版), 2023, 18(06): 480-484.
[4] 陈永沛, 仲海燕, 陈勇, 王慜, 王倩, 邹鸣立, 袁斯明. 数字减影血管造影在腓动脉穿支皮瓣移植中的应用[J]. 中华损伤与修复杂志(电子版), 2023, 18(06): 507-510.
[5] 韩李念, 王君. 放射性皮肤损伤治疗的研究进展[J]. 中华损伤与修复杂志(电子版), 2023, 18(06): 533-537.
[6] 刘竹影, 周年苟, 李泳祺, 周丽斌. 空心环钻联合手术导板用于自体牙移植牙槽窝备洞[J]. 中华口腔医学研究杂志(电子版), 2023, 17(06): 418-423.
[7] 中华医学会器官移植学分会, 中国医师协会器官移植医师分会, 上海医药行业协会. 中国肝、肾移植受者霉酚酸类药物应用专家共识(2023版)[J]. 中华移植杂志(电子版), 2023, 17(05): 257-272.
[8] 江文诗, 何湘湘. 全球及我国器官捐献发展特征分析与学科建设[J]. 中华移植杂志(电子版), 2023, 17(05): 280-286.
[9] 严庆, 刘颖, 邓斐文, 陈焕伟. 微血管侵犯对肝癌肝移植患者生存预后的影响[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 624-629.
[10] 廖梅, 张红君, 金洁玚, 吕艳, 任杰. 床旁超声造影对肝移植术后早期肝动脉血栓的诊断价值[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 630-634.
[11] 李秉林, 吕少诚, 潘飞, 姜涛, 樊华, 寇建涛, 贺强, 郎韧. 供肝灌注液病原菌与肝移植术后早期感染的相关性分析[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 656-660.
[12] 吕垒, 冯啸, 何凯明, 曾凯宁, 杨卿, 吕海金, 易慧敏, 易述红, 杨扬, 傅斌生. 改良金氏评分在儿童肝豆状核变性急性肝衰竭肝移植手术时机评估中价值并文献复习[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 661-668.
[13] 何吉鑫, 杨燕妮, 王继伟, 李建国, 谢铭. 肠道菌群及肠道代谢产物参与慢性便秘发生机制的研究进展[J]. 中华结直肠疾病电子杂志, 2023, 12(06): 495-499.
[14] 郭晓磊, 李晓云, 孙嘉怿, 金乐, 郭亚娟, 史新立. 含生长因子骨移植材料的研究进展和监管现状[J]. 中华老年骨科与康复电子杂志, 2023, 09(06): 373-378.
[15] 王丁然, 迟洪滨. 自身免疫甲状腺炎对子宫内膜异位症患者胚胎移植结局的影响[J]. 中华临床医师杂志(电子版), 2023, 17(06): 682-688.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号