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Dl-3-n-butylphthalide Attenuates Spinal Cord Injury via Regulation of MMPs and Junction Proteins in Mice

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Abstract

As a serious trauma of the neurological system, spinal cord injury (SCI) results in permanent disability, gives rise to immediate vascular damage and a wide range of matters that induce the breakage of blood spinal cord barrier (BSCB). SCI activates the expression of MMP-2/9, which are considered to accelerate the disruption of BSCB. Recent research shows that Dl-3-n-butylphthalide (NBP) exerted protective effects on blood spinal cord barrier in animals after SCI, but the underlying molecular mechanism of NBP on the BSCB undergoing SCI is unknown. Here, our research show that NBP inhibited the expression of MMP-2/9, then improved the permeability of BSCB following SCI. After the T9 level of spinal cord performed with a moderate injury, NBP was managed by intragastric administration and further performed once a day. NBP remarkably improved the permeability of BSCB and junction proteins degration, then promoted locomotion recovery. The protective effect of NBP on BSCB destruction is related to the regulation of MMP-2/9 induced by SCI. Moreover, NBP obviously inhibited the MMP-2/9 expression and junction proteins degradation in microvascular endothelial cells. In conclusion, our results indicate that MMP-2/9 are relevant to the breakdown of BSCB, NBP impairs BSCB destruction through inhibiting MMP-2/9 and promotes functional recovery subjected to SCI. NBP is likely to become a new nominee as a therapeutic to treat SCI via a transigent BSCB.

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Acknowledgements

This research was partly sustained by appropriation from Basic Public welfare Research Project of Zhejiang Province (LGF18H060011), Medical Science and Technology Project of Zhejiang (2020KY347,2021KY1225) and by Science and Technology Planning Program of Taizhou City (20ywa22), Science and Technology Planning Program of Enze (20EZC31).

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Authors and Affiliations

  1. Department of Orthopaedics, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, 317000, Zhejiang, People’s Republic of China

    Binbin Zheng, Shuang Mi, Wei Xu, Xiangdong Yang, Zhenghua Hong & Zhangfu Wang

  2. Nursing Department, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, 317000, Zhejiang, People’s Republic of China

    Yanjun Jin

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  1. Binbin Zheng
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  2. Yanjun Jin
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Zheng, B., Jin, Y., Mi, S. et al. Dl-3-n-butylphthalide Attenuates Spinal Cord Injury via Regulation of MMPs and Junction Proteins in Mice. Neurochem Res 46, 2297–2306 (2021). https://doi.org/10.1007/s11064-021-03361-7

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