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Transplantation of NSCs Promotes the Recovery of Cognitive Functions by Regulating Neurotransmitters in Rats with Traumatic Brain Injury

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Abstract

Transplantation of neural stem cells (NSCs) may be a potential strategy for traumatic brain injury treatment (TBI) due to their intrinsic advantages, such as cell replacement, secretion of neurotrophins and formation of functional synapses with host. However the underlying effects of transplanted NSCs on host micro-environment still need to be further elucidated. In this manuscript the effects of NSCs on release of neurotransmitter, survival of hippocampal neurons, reactivity of astrocytes and recovery of cognitive function after TBI were observed. The NSCs were isolated from cortex of neonatal Sprague–Dawley rat and then transplanted into injured brain regions caused by free-weight drop. The proliferation of astrocytes around injured sites were examined by GFAP immunofluorescent staining on 3, 7, 14 days after injury. The survival of neurons at CA1 regions of hippocampus toward contused regions was observed by HE staining on 3 and 14 days post-injury. The content of glutamic acid (Glu) and GABA in hippocampal tissues was examined on 1, 3, 7, 14, 28 days after injury by ELISA. On third day post-injury, hippocampal-dependent spatial memory was measured for 5 days without intermittent. NSCs in culture have the ability to proliferate and differentiate into different phenotypes of neural cells. After transplantation of NSCs, the proliferation of astrocytes around injured site was significantly inhibited compared to the injured group. At the same time the survival of neurons in hippocampal CA1 region were much more than those in injured group on 14 days post-injury. Meanwhile, the cognitive functions in NSC transplanted group was remarkably improved compared with injured group (p < 0.05). Furthermore, NSCs transplantation dramatically inhibited the release of Glu and maintained the content of GABA in injured hippocampal tissues on 1, 3, 7, 14, 28 days post-injury, which was of difference in statistics (p < 0.05). NSCs transplantation can effectively alleviate the formation of glial scar, enhance the survival of hippocampal neurons and improve cognitive function defects in rats with TBI. The underlying mechanism may be related to their effects on inhibiting the release of Glu and maintaining the content of GABA, so as to down-regulate excitotoxicity of neurotransmitter and improve the micro-environment in injured sites.

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Funding

Funding was provided by Qinnian Peiyu project of Military (Grant No. 16QNP105) and national natural scientific fund of China (Grant No. 81772066).

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Author notes

  1. Mei-ling Luo and Lu Pan contributed equally to the work.

Authors and Affiliations

  1. Research Institute of Surgery, Daping Hospital, the Army Military Medical University, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing, 400042, China

    Mei-ling Luo, Lu Pan, Li Wang, Hai-yan Wang, Sen Li, Zai-yun Long, Lin Zeng & Yuan Liu

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  1. Mei-ling Luo
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  2. Lu Pan
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  3. Li Wang
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  4. Hai-yan Wang
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  6. Zai-yun Long
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  7. Lin Zeng
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  8. Yuan Liu
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Correspondence to Yuan Liu.

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11064_2019_2897_MOESM5_ESM.ppt

Supplementary material 5 Supplemented Fig. 1. The labeled NSCs in brain tissue after transplantation. A. Location and migration of NSCs labeled by DAPI in the host brain 7 days post transplantation. (bar = 250 um). B. Location and migration of NSCs labeled by DAPI in the host brain 14 days post transplantation. (bar = 250 um) (PPT 973 kb)

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Luo, Ml., Pan, L., Wang, L. et al. Transplantation of NSCs Promotes the Recovery of Cognitive Functions by Regulating Neurotransmitters in Rats with Traumatic Brain Injury. Neurochem Res 44, 2765–2775 (2019). https://doi.org/10.1007/s11064-019-02897-z

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  • DOI: https://doi.org/10.1007/s11064-019-02897-z

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