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

doi:10.3877/cma.j.issn.2095-9141.2017.06.008

Abstract

Abstract:

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

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.

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References 19

[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.

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±2.04^a	21.95±1.94^a	21.29±1.96^a
PBS处理组	6	29.39±2.89^ab	29.50±2.27^ab	16.45±1.52^ab
F值	?	296.320	131.030	424.000
P值	?	0.000	0.000	0.000

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±2.04^a	21.95±1.94^a	21.29±1.96^a
PBS处理组	6	29.39±2.89^ab	29.50±2.27^ab	16.45±1.52^ab
F值	?	296.320	131.030	424.000
P值	?	0.000	0.000	0.000

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