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. 2018 Aug;43(8):1641-1649.
doi: 10.1007/s11064-018-2580-1. Epub 2018 Jun 22.

Knockdown of MicroRNA-21 Promotes Neurological Recovery After Acute Spinal Cord Injury

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Knockdown of MicroRNA-21 Promotes Neurological Recovery After Acute Spinal Cord Injury

Wei Xie et al. Neurochem Res. .

Abstract

To assess the therapeutic effects of microRNA-21 (miR-21) knockdown (KD) for acute thoracic spinal cord contusion using a mouse model. Forty C57/BL6 mice were randomly divided into four groups: mice in the sham-operated (Sham) group received surgical procedure without spinal cord contusion; the spinal cord injury (SCI) group mice underwent spinal cord contusion without treatment; mice in the miR-21 KD group underwent spinal cord contusion followed by a single dose subdural injection of miR-21 KD vectors (1 × 107 TU); and the negative control (NC) group mice were given subdural injection of comparable amount of NC vectors (1 × 107 TU) after spinal cord contusion. The Basso Mouse Scale (BMS) was employed to assess hindlimb motor functions. Hematoxylin-eosin and Luxol fast blue staining were performed to evaluate pathologic changes in spinal cord tissues. Peripheral blood serum levels of tumor necrosis factor α (TNFα), transforming growth factor β (TGF-β) and interleukin-1β (IL-1β) were determined by the enzyme-linked immunosorbent assay, and mRNA expression of Brain derived neurotrophic factor (BDNF) was examined by reverse transcription-polymerase chain reaction (RT-PCR). Western blotting was performed to analyze the AKT signaling pathway. KD of miRNA-21 effectively improved the BMS scores at day 14 post-surgery compared with the SCI group (p < 0.01). The spinal cord tissue in the miR-21 KD group displayed the most overt histologic signs of recovery, with axonal regeneration and the recovery of neuronal morphology at day 14 post-surgery. Significantly alleviation of TGF-β1, TNF-α and IL-1β was also found in sera from the miR-21 inhibition group in comparison to others, whereas BDNF gene expression was upregulated following miR-21 KD (p < 0.01). Further, significantly decreased AKT phosphorylation activity was illustrated in the miR-21 KD group (p < 0.001). The data suggest that miR-21 KD significantly reduces the inflammatory response at the damaged spinal cord site and promotes motor functional recovery. The treatment also elevated expression of BDNF, a neurotrophin participating in nerve regeneration.

Keywords: MiR-21; Mouse; Signaling pathway; Spinal cord injury.

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