PMID- 29934690 OWN - NLM STAT- MEDLINE DCOM- 20190401 LR - 20190401 IS - 1573-6903 (Electronic) IS - 0364-3190 (Linking) VI - 43 IP - 8 DP - 2018 Aug TI - Knockdown of MicroRNA-21 Promotes Neurological Recovery After Acute Spinal Cord Injury. PG - 1641-1649 LID - 10.1007/s11064-018-2580-1 [doi] AB - 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 x 10(7) TU); and the negative control (NC) group mice were given subdural injection of comparable amount of NC vectors (1 x 10(7) 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 alpha (TNFalpha), transforming growth factor beta (TGF-beta) and interleukin-1beta (IL-1beta) 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-beta1, TNF-alpha and IL-1beta 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. FAU - Xie, Wei AU - Xie W AD - Department Spinal Surgery, Jinan Central Hospital Affiliated to Shandong University, 105 Jiefang Road, Jinan, 250013, Shandong, China. AD - Department Emergency Medicine, Taishan Medical University, Taian, 271016, Shandong, China. FAU - Yang, Shang-You AU - Yang SY AD - Department Surgery - Orthopedics, University of Kansas School of Medicine-Wichita, Wichita, KS, 67214, USA. FAU - Zhang, Qianqian AU - Zhang Q AD - Department Obstetrics and Gynecology, Affiliated Hospital of Taishan Medical University, Taian, 271000, Shandong, China. FAU - Zhou, Yadong AU - Zhou Y AD - Department Emergency Medicine, Taishan Medical University, Taian, 271016, Shandong, China. FAU - Wang, Yi AU - Wang Y AD - Department Ophthalmology, Affiliated Hospital of Taishan Medical University, Taian, 271000, Shandong, China. FAU - Liu, Ronghan AU - Liu R AD - Department Spinal Surgery, Jinan Central Hospital Affiliated to Shandong University, 105 Jiefang Road, Jinan, 250013, Shandong, China. FAU - Wang, Wenzhao AU - Wang W AD - Department Spinal Surgery, Jinan Central Hospital Affiliated to Shandong University, 105 Jiefang Road, Jinan, 250013, Shandong, China. FAU - Shi, Jixue AU - Shi J AD - Department Emergency Medicine, Taishan Medical University, Taian, 271016, Shandong, China. FAU - Ning, Bin AU - Ning B AUID- ORCID: 0000-0002-7592-9485 AD - Department Spinal Surgery, Jinan Central Hospital Affiliated to Shandong University, 105 Jiefang Road, Jinan, 250013, Shandong, China. ningbin@sdu.edu.cn. FAU - Jia, Tanghong AU - Jia T AD - Department Spinal Surgery, Jinan Central Hospital Affiliated to Shandong University, 105 Jiefang Road, Jinan, 250013, Shandong, China. LA - eng GR - 81401014/National Natural Science Foundation of China/ GR - 81771346/National Natural Science Foundation of China/ GR - BS2013YY049/Distinguished Middle-Aged and Young Scientist Encourage and Reward Foundation of Shandong Province/ GR - 2012M511036/China Postdoctoral Science Foundation/ PT - Journal Article DEP - 20180622 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cytokines) RN - 0 (MIRN21 microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics MH - Cytokines/metabolism MH - Female MH - Gene Expression Regulation/genetics MH - Gene Knockdown Techniques MH - Genetic Therapy/methods MH - Mice, Inbred C57BL MH - MicroRNAs/*genetics MH - Nerve Regeneration/*genetics MH - Proto-Oncogene Proteins c-akt/metabolism MH - RNA, Messenger/genetics MH - Signal Transduction/physiology MH - Spinal Cord/pathology MH - Spinal Cord Injuries/pathology/*therapy OTO - NOTNLM OT - MiR-21 OT - Mouse OT - Signaling pathway OT - Spinal cord injury EDAT- 2018/06/24 06:00 MHDA- 2019/04/02 06:00 CRDT- 2018/06/24 06:00 PHST- 2017/09/24 00:00 [received] PHST- 2018/06/19 00:00 [accepted] PHST- 2018/06/13 00:00 [revised] PHST- 2018/06/24 06:00 [pubmed] PHST- 2019/04/02 06:00 [medline] PHST- 2018/06/24 06:00 [entrez] AID - 10.1007/s11064-018-2580-1 [pii] AID - 10.1007/s11064-018-2580-1 [doi] PST - ppublish SO - Neurochem Res. 2018 Aug;43(8):1641-1649. doi: 10.1007/s11064-018-2580-1. Epub 2018 Jun 22.