Electrical stimulation combined with neurotrophin 3 promotes
proliferation and differentiation of endogenous neural stem cells after spinal
cord injury in rats

doi:10.3969/j.issn.2095-4344.2019

Abstract

Abstract:

BACKGROUND: Due to limited access to exogenous neural stem cells, immune rejection and ethical problems, how to activate endogenous neural stem cells and promote their growth, proliferation and differentiation has become an issue of concern.

OBJECTIVE: To investigate the effects of electrical stimulation combined with neurotrophin 3 on the proliferation and differentiation of endogenous neural stem cells into neurons after spinal cord injury in rats.

METHODS: Ninety-six rats were randomly divided into sham operation (spinal cord exposed only), spinal cord injury, electrical stimulation, and electrical stimulation+neurotrophin groups, 24 rats in each group. A rat model of spinal cord injury was established by modified Allen method in the latter three groups. After the model was established, the rats in the four groups were given corresponding treatments. At 7, 14, 21, and 28 days after modeling, the motor function of hind limbs was evaluated by Basso-Beattie-Bresnahan score. The latency of motor evoked potential was examined by electrophysiology. At 28 days after modeling, samples of the spinal cord were taken for hematoxylin-eosin staining to observe the pathological changes and for immunohistochemical staining to observe the the proliferation and differentiation of endogenous neural stem cells. The study was approved by the Ethics Committee of the Second Hospital of Lanzhou University.

RESULTS AND CONCLUSION: (1) Compared with the sham operation group, the Basso-Beattie-Bresnahan score in the spinal cord injury group was significantly decreased (P < 0.01), and a large number of inflammatory cells infiltrated into the spinal cord tissues with multiple cavities. Compared with the spinal cord injury group, the hind limb function in the electrical stimulation and electrical stimulation+neurotrophin groups began to recover gradually. Basso-Beattie-Bresnahan score in the electrical stimulation+neurotrophin group was significantly higher than that in the electrical stimulation group (P < 0.05). The above pathological changes were significantly improved. (2) No latency of motor evoked potentials in both hind limbs was detected in the spinal cord injury group at 7, 14 days and in the electrical stimulation group at 7 days, respectively. At 21 and 28 days, the latency of motor evoked potential was shorter in the electrical stimulation and electrical stimulation+neurotrophin groups than in the spinal cord injury group (P < 0.05); and the latency of motor evoked potential in the electrical stimulation+neurotrophin group was shorter than that in the electrical stimulation group (P < 0.05). (3) The number of BrdU and Nestin positive cells and the expression of microtubule-associated protein 2 were ranked as follows: electrical stimulation+neurotrophin group > electrical stimulation group > spinal cord injury group. The expression level of glial fibrillary acidic protein was highest in the spinal cord injury group, followed by electrical stimulation group, and lowest in the electrical stimulation+neurotrophin group. These results show that after electrical stimulation plus neurotrophin 3 intervention, endogenous neural stem cells can proliferate and differentiate into neurons. Pathological damage is significantly alleviated and motor function of hind limbs is significantly improved.

Key words: spinal cord injury, endogenous neural stem cells, electrical stimulation, neurotrophin 3, cell proliferation, cell differentiation, motor function

CLC Number:

Zhang Peigen, Heng Xiaolai, Xie Di, Wang Jin, Ma Jinglin, Kang Xuewen. Electrical stimulation combined with neurotrophin 3 promotes proliferation and differentiation of endogenous neural stem cells after spinal cord injury in rats[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(7): 1076-1082.

Figures/Tables 6

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