Transplantation of induced neural stem cells receiving CR2-Crry pre-treatment mediates neuroprotection following brain injury

doi:10.3877/cma.j.issn.2095-123X.2021.04.006

Abstract

Abstract:

Objective

To study the effects of transplanted induced neural stem cells (iNSCs) receiving CR2-Crry pre-treatment on neuroprotection following brain injury.

Methods

Healthy adult male C57BL/6 mouse brain injury models were established and mice having an neurological severity scores (NSS) of 4-8 were enrolled in brain injury group (n=18). These brain injury animals were randomly divided into 3 groups: the CR2-Crry-iNSC group (n=6), the phosphate buffered solution (PBS)-iNSC group (n=6) and the PBS group (n=6). At 12 h after brain injury, CR2-Crry-iNSCs, PBS-iNSCs or PBS were separately injected into the brains of brain injury mice via stereotactic method. On day 14 after brain injury, mice were sacrificed for morphological analysis. Immunofluorescent staining and TdT-mediated dUTP nick and labeling (TUNEL) staining were utilized to determine the effects of CR2-Crry-iNSC and PBS-iNSC grafts on Crry⁺/NeuN⁺ and NeuN⁺/TUNEL⁺ cells in the brains of brain injury mice.

Results

Double-labeling experiments revealed that the level of Crry⁺/NeuN⁺ neurons in the brains of the PBS group was significantly lower than that in CR2-Crry-iNSC and PBS-iNSC groups (P<0.05). Furthermore, the level of Crry⁺/NeuN⁺ neurons was substantially higher in the CR2-Crry-iNSC group than in the PBS-iNSC group (P<0.05). In contrast, TUNEL staining showed that the level of NeuN⁺/TUNEL⁺ neurons in the brains of the PBS group was significantly higher than that in CR2-Crry-iNSC and PBS-iNSC groups (P<0.05). Moreover, the level of NeuN⁺/TUNEL⁺ neurons was substantially lower in the CR2-Crry-iNSC group than in the PBS-iNSC group (P<0.05).

Conclusion

Transplantation of iNSCs receiving CR2-Crry pre-treatment could increase the levels of Crry expression in neurons and alleviate complement-mediated neuronal damage following brain injury.

Key words: Brain injury, Induced neural stem cell, Complement activation, Complement regulation, Transplantation

Mou Gao, Ruxiang Xu, Qin Dong, Lili Guo. Transplantation of induced neural stem cells receiving CR2-Crry pre-treatment mediates neuroprotection following brain injury[J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2021, 11(04): 215-220.

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Figures/Tables 3

References 19

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组别	只数	Crry/NeuN双阳性神经细胞	TUNEL/NeuN双阳性神经细胞
PBS组	6	19.43±2.12	25.95±2.64
PBS-iNSCs组	6	36.12±3.81^a	15.68±1.69^a
CR2-Crry-iNSCs组	6	50.01±5.45^ab	9.08±0.97^ab
F值		86.554	120.841
P值		<0.001	<0.001

组别	只数	Crry/NeuN双阳性神经细胞	TUNEL/NeuN双阳性神经细胞
PBS组	6	19.43±2.12	25.95±2.64
PBS-iNSCs组	6	36.12±3.81^a	15.68±1.69^a
CR2-Crry-iNSCs组	6	50.01±5.45^ab	9.08±0.97^ab
F值		86.554	120.841
P值		<0.001	<0.001

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