Neurotrophic effects of induced neural stem cell grafts following traumatic brain injury

doi:10.3877/cma.j.issn.2095-123X.2019.02.009

Abstract

Abstract:

Objective

To study the neurotrophic effects of grafted induced neural stem cells (iNSCs) following traumatic brain injury (TBI).

Methods

Healthy adult male C57BL/6 mouse TBI models were established using a standardized weight-drop device. Mice having an neurological severity scores (NSS) of 4-8 were randomly assigned to two groups: the iNSC group (n=12) and the phosphate buffered solution (PBS) group (n=9). Sham-operated mice underwent the same procedures, but not head trauma (n=9). At 12 h post-injury, iNSCs (1×10⁶ cells) or PBS were separately injected into the brains of TBI mice via stereotactic method. On day 7 after TBI, animals were sacrificed for molecular-biological and morphological analysis. RT-qPCR and ELISA were utilized to determine the levels of BDNF and GDNF expression. To explore the neurotrophic effects of iNSCs, we utilized immunofluorescent staining to detect the expression of BDNF and GDNF in iNSC grafts.

Results

RT-qPCR assay revealed that the expression levels of Bdnf and Gdnf were significantly lower in the TBI group than in the sham group (P<0.05). Furthermore, the levels of Bdnf and Gdnf expression were significantly higher in the iNSC group than in the PBS group (P<0.05). ELISA indicated that the expression levels of BDNF and GDNF were significantly lower in the TBI group than in the sham group (P<0.05). Furthermore, the levels of BDNF and GDNF expression were significantly higher in the iNSC group than in the PBS group (P<0.05). Immunofluorescent staining showed that GFP-labelling iNSCs migrated to the damaged area and expressed BDNF and GDNF.

Conclusion

Stereotactic transplantation of iNSCs can express BDNF and GDNF to play neurotrophic effects following TBI.

Key words: Induced neural stem cell, Traumatic brain injury, Brain-derived neurotrophic factor, Glial cell-line derived neurotrophic factor, Transplantation

Mou Gao, Ruxiang Xu, Wenjia Wang, Qin Dong, Boyun Ding, Hui Yao, Zhijun Yang. Neurotrophic effects of induced neural stem cell grafts following traumatic brain injury[J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2019, 09(02): 101-105.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhnkjbykfzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-123X.2019.02.009

https://zhnkjbykfzz.cma-cmc.com.cn/EN/Y2019/V09/I02/101

Figures/Tables 3

References 16

[1]	Simon DW, Mcgeachy MJ, Bayır H, et al. The far-reaching scope of neuroinflammation after traumatic brain injury[J]. Nat Rev Neurol,2017, 13(3): 171-191.
[2]	Zetterberg H, Blennow K. Fluid biomarkers for mild traumatic brain injury and related conditions[J]. Nat Rev Neurol, 2016, 12(10): 563-574
[3]	Corps KN, Roth TL, McGavern DB. Inflammation and neuroprotection in traumatic brain injury[J]. JAMA Neurol, 2015, 72(3): 355-362.
[4]	Galluzzi L, Bravo-San Pedro JM, Blomgren K, et al. Autophagy in acute brain injury[J]. Nat Rev Neurosci, 2016, 17(8): 467-484.
[5]	Gao M, Dong Q, Yao H, et al. Induced neural stem cells modulate microglia activation states via CXCL12/CXCR4 signaling[J]. Brain Behav Immun, 2017, 59: 288-299.
[6]	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.
[7]	Carney N, Totten AM, O’Reilly C, et al. Guidelines for the management of severe traumatic brain injury, fourth edition[J]. Neurosurgery, 2017, 80(1): 6-15.
[8]	Maas AIR, Menon DK, Adelson PD, et al. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research[J]. Lancet Neurol, 2017, 16(12): 987-1048.
[9]	Bramlett HM, Dietrich WD. Long-term consequences of traumatic brain injury: current status of potential mechanisms of injury and neurological outcomes[J]. J Neurotraum, 2015, 32(23): 1834-1848.
[10]	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.
[11]	Koutsoudaki PN, Papastefanaki F, Stamatakis A, et al. Neural stem/progenitor cells differentiate into oligodendrocytes, reduce inflammation, and ameliorate learning deficits after transplantation in a mouse model of traumatic brain injury[J]. Glia, 2016, 64(5): 763-779.
[12]	Anderson ST, Commins S, Moynagh PN, et al. Lipopolysaccharide-induced sepsis induces long-lasting affective changes in the mouse[J]. Brain Behav Immun, 2015, 43: 98-109.
[13]	Ager RR, Davis JL, Agazaryan A, et al. Human neural stem cells improve cognition and promote synaptic growth in two complementary transgenic models of alzheimer’s disease and neuronal loss[J]. Hippocampus, 2015, 25(7): 813-826.
[14]	Cordero-Llana O, Rinaldi F, Brennan PA, et al. Galanin promotes neuronal differentiation from neural progenitor cells in vitro and contributes to the generation of new olfactory neurons in the adult mouse brain[J]. Exp Neurol, 2014, 256: 93-104.
[15]	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.
[16]	高谋，徐如祥，王海峰,等.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, 3(6): 355-359.

组别	只数	Bdnf基因转录水平	Gdnf基因转录水平
sham组	3	2.39±0.25	2.33±0.25
iNSCs移植组	3	1.89±0.21^a	1.72±0.16^a
PBS处理组	3	1.01±0.13^ab	1.00±0.12^ab
F值	?	35.69	50.53
P值	?	0.000	0.000

组别	只数	Bdnf基因转录水平	Gdnf基因转录水平
sham组	3	2.39±0.25	2.33±0.25
iNSCs移植组	3	1.89±0.21^a	1.72±0.16^a
PBS处理组	3	1.01±0.13^ab	1.00±0.12^ab
F值	?	35.69	50.53
P值	?	0.000	0.000

组别	只数	BDNF蛋白表达水平	GDNF蛋白表达水平
sham组	6	49.73±4.85	41.05±3.94
iNSCs移植组	6	36.01±3.36^a	34.84±3.24^a
PBS处理组	6	20.79±2.09^ab	16.77±1.55^ab
F值	?	96.320	100.740
P值	?	0.000	0.000

组别	只数	BDNF蛋白表达水平	GDNF蛋白表达水平
sham组	6	49.73±4.85	41.05±3.94
iNSCs移植组	6	36.01±3.36^a	34.84±3.24^a
PBS处理组	6	20.79±2.09^ab	16.77±1.55^ab
F值	?	96.320	100.740
P值	?	0.000	0.000

Please choose a citation manager

Content to export