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. 2014 Dec 15;7(12):4967-74.
eCollection 2014.

Neuroprotective effect of bone marrow stromal cell combination with atorvastatin in rat model of spinal cord injury

Fang Li  1 , Dan Fei  2 , Libo Sun  2 , Sixun Zhang  1 , Yue Yuan  1 , Li Zhang  1 , Kuiming Zhao  1 , Rui Li  1 , Yanbing Yu  1
Affiliations

Neuroprotective effect of bone marrow stromal cell combination with atorvastatin in rat model of spinal cord injury

Fang Li et al. Int J Clin Exp Med. .

Abstract

The aims of this study was to assessed the ability of a combination treatment of bone marrow stromal cell (BMSC) and atorvastatin in a rat model of spinal cord injury (SCI) as an appropriate substitute for current SCI treatments. In the present study, the female Wistar rats were divided into five groups (n = 20) after SCI by New York University Device: SCI, sham, atorvastatin, graft BMSC and graft BMSC plus atorvastatin. Locomotion was assessed using Basso, Beattie and Bresnahan (BBB) test and walking test after SCI. In addition, microvessel density (MVD) was calculated by immunohistochemistry after SCI. We also investigate the vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) expression level by western blot after drug treatment. The results showed that BBB scores and walking test were increased in atorvastatin plus BMSC group compared to single atorvastatin and BMSC groups (P < 0.05). In addition, MVD also significantly increased in combination group compared to single treatment group. Compared to sole drug, VEGF and BDNF expression were significantly up-regulated in atorvastatin combination with BMSC group (P < 0.05). These results imply that the combined use of atorvastatin and BMSC treatment may represent a promising strategy for clinically applicable pharmacological therapy for initiation of neuroprotection after SCI.

Keywords: Spinal cord injury; atorvastatin; bone marrow stromal cells; neuroprotective.

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Figures

Figure 1
Figure 1
Bone marrow stromal cells culture and detection. A: Third passage of bone marrow mesenchymal stem cells (BMSCs) were observed using inverted phase contrast microscope. B: The expression of CD44 in BMSCs was observed by phase contrast the inverted microscope.
Figure 2
Figure 2
Effects of BMSC combination with atorvastatin on MPO activity. Following the injury, MPO activity in spinal cord from SCI mice was significantly increased at 24 h after the damage in comparison to sham mice. Treatment with BMSC and atorvastatin significantly reduced the SCI-induced increase in MPO activity. A single treatment did not reduce the neutrophil infiltration in the injured spinal cord. *P < 0.05 versus SCI group, #P < 0.05 versus BMSC group.
Figure 3
Figure 3
Combination treatment of BMSC and atorvastatin improved functional recovery after SCI. A: BBB tests were performed in different groups at different time after treatment; B: Grid walking test was evaluated in different groups 35 days after treatment; showed that the percentages of missteps in combining treated group were significantly lower than the control group.**P < 0.05 as compared to SCI group, #P < 0.05 as compared to BMSC group.
Figure 4
Figure 4
The microvessel density (MVD) level was measured in different groups 35 days after treatment using single BMSC and atorvastatin or both, *P < 0.05 as compared to SCI group, #P < 0.05 as compared to BMSC group.
Figure 5
Figure 5
Effect of BMSC combination with atorvastatin on the expression of VEGF and BDNF in the injured spinal cord. The expression of BDNF and VEGF in the treatment group was significantly higher than SCI group; the expression of BDNF and VEGF in the BMSC combination with atorvastatin group was significantly higher than those of single BMSC group and atorvastatin group. *P < 0.05 as compared to SCI group, #P < 0.05 as compared to BMSC group.
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