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| 1 | Temporal changes in inflammatory mitochondria-enriched microRNAs following traumatic brain injury and effects of miR-146a nanoparticle delivery显示文摘MicroRNAs(miRNAs)are small non-coding RNA molecules that regulate post-transcriptional gene expression and contribute to all aspects of cellular function.We previously reported that the activities of several mitochondria-enriched miRNAs regulating inflammation(i.e.,miR-142-3p,miR-142-5p,and miR-146a)are altered in the hippocampus at 3–12 hours following a severe traumatic brain injury.In the present study,we investigated the temporal expression profile of these inflammatory miRNAs in mitochondria and cytosol fractions at more chronic post-injury times following severe controlled cortical impact injury in rats.In addition,several inflammatory genes were analyzed in the cytosol fractions.The analysis showed that while elevated levels were observed in cytoplasm,the mitochondria-enriched miRNAs,miR-142-3p and miR-142-5p continued to be significantly reduced in mitochondria from injured hippocampi for at least 3 days and returned to near normal levels at 7 days post-injury.Although not statistically significant,miR-146a also remained at reduced levels for up to 3 days following controlled cortical impact injury,and recovered by 7 days.In contrast,miRNAs that are not enriched in mitochondria,including miR-124a,miR-150,miR-19b,miR-155,and miR-223 were either increased or demonstrated no change in their levels in mitochondrial fractions for 7 days.The one exception was that miR-223 levels were reduced in mitochondria at 1 day following injury.No major alterations were observed in sham operated animals.This temporal pattern was unique to mitochondria-enriched miRNAs and correlated with injury-induced changes in mitochondrial bioenergetics as well as expression levels of several inflammatory markers.These observations suggested a potential compartmental re-distribution of the mitochondria-enriched inflammatory miRNAs and may reflect an intracellular mechanism by which specific miRNAs regulate injury-induced inflammatory signaling.To test this,we utilized a novel peptide-based nanoparticle strategy for in vitro and in vivo delivery of a miR-146a mimic as a potential therapeutic strategy for targeting nuclear factor-kappa B inflammatory modulators in the injured brain.Nanoparticle delivery of miR-146a to BV-2 or SH-SY5Y cells significantly reduced expression of TNF receptor-associated factor 6(TRAF6)and interleukin-1 receptor-associated kinase 1(IRAK1),two important modulators of the nuclear factor-kappa B(NF-κB)pro-inflammatory pathway.Moreover,injections of miR-146a containing nanoparticles into the brain immediately following controlled cortical impact injury significantly reduced hippocampal TNF receptor-associated factor 6 and interleukin-1 receptor-associated kinase 1 levels.Taken together,our studies demonstrate the subcellular alteration of inflammatory miRNAs after traumatic brain injury and establish proof of principle that nanoparticle delivery of miR-146a has therapeutic potential for modulating pro-inflammatory effectors in the injured brain.All of the studies performed were approved by the University of Kentucky Institutional Animal Care and Usage Committee(IACUC protocol#2014-1300)on August 17,2017. | Wang-Xia Wang Paresh Prajapati Hemendra J.Vekaria Malinda Spry Amber L.Cloud Patrick G.Sullivan Joe E.Springer | 2021 | Neural Regeneration Research2021，16，3： | 3 |
| 2 | Intelligent cruise-control applications-real-time,embedded hybrid control software显示文摘 | Girard A R Spry S Hedrick J K | 2005 | IEEE Robotics & Automation Magazine2005，12，1： | 1 |
| 3 | Less pain does equal better quality of life following strontium-89 therapy for metastatic prostate cancer显示文摘 | Turner S L Gruenewald S Spry N | 2001 | Br J Cancer2001，84，3： | 1 |
| 4 | 24 -hour monitoring of intraocular pressure in glaucoma man agement:A Retrospective Review显示文摘 | Hughes E Spry P Diam ond J | 2003 | J Glaucoma2003，12，3： | 1 |
| 5 | Intelligent cruise-control applications-real-time embedded hybrid control software显示文摘 | Girard A R Spry S Hedrick J K | 2005 | IEEE Robotics & Automation Magazine2005，12，1： | 1 |
| 6 | Direct dating of MVT mineralization: Use of Sm-Nd in fluorite 显示文摘 | Chesley J T Halliday A N Kyser T K Spry P G | 1994 | Economic Geology1994，89，： | 1 |
| 7 | The Effects of Fiscal Competition on Local Property and Income Tax Reliance显示文摘 | John Arthur Spry | 2005 | Topics in Economic Analysis & Policy2005，5，1： | 1 |
| 8 | 24-hour monitoring of intra- ocular pressure in glaucoma management: a retrospective review 显示文摘 | Hughes E Spry P Diamond J | 2003 | J Glaucoma2003，12，： | 1 |
| 9 | 3D radiotherapy can be safely combined with sandwich systemic gemcit- abine chemotherapy in the management of pancreatic cancer: factors influencing outcome 显示文摘 | Spry N Harvey J Macleod C | 2008 | Int J Radiat Oncol Biol Phys2008，70，5： | 1 |
| 10 | Adverse effects to quality of life arising from treatment can recover with intermittent androgen suppression in men with prostate cancer显示文摘 | Spry NA Kristjanson L Hooton B | 2006 | Eur J Cancer2006，42，8： | 1 |
| 11 | Carnitine treatment improved quality-of-life measure in a sample of Midwest- ern hemodialysis patients 显示文摘 | Steiber AL Davis AT Spry L | 2006 | JPEN J Parenter Enteral Nutr2006，30，： | 1 |
| 12 | Identification of progressive glaueomatous visual field loss显示文摘 | Spry PG Johnson CA | 2002 | Surv Ophthalmol2002，47，： | 1 |
| 13 | Purification of normal human eosinophils using the different binding capacities of blood leucocytes of complexed rabbit IgG 显示文摘 | Tai PC Spry CJ | 1977 | Clin Exp Immunol1977，28，2： | 1 |
| 14 | Electrostatic self-assembly as a means to create organic photovoltaic devices显示文摘 | Durstocka M F Taylor B Spry R J | 2001 | Synthetic Metals2001，，116： | 1 |
| 15 | Stable electrical oper- ation of 6H-SiC JFETs and ICs for thousands of hours at 500℃显示文摘 | Neudeck P G Spry D J Chen L Y | 2008 | IEEE Electron Device Letters2008，29，5： | 1 |
| 16 | Shallow Submarine Epithermal Pb-Zn-Cu-Au-Ag-Te Mineralization on Western Milos Island, Aegean Volcanic Arc, Greece: Mineralogical, Geological and Geochemical Constraints 显示文摘 | Alfieris D Voudouris P Spry P G | 2013 | Ore Geology Reviews2013，53，： | 1 |
| 17 | Combined resistance and aerobic exercise program reverses muscle loss in men undergoing an- drogen suppression therapy for prostate cancer without bone metastases: a randomized controlled trial 显示文摘 | Ga|vao DA Taaffe DR Spry N | 2010 | J Clin Oncol2010，28，2： | 1 |
| 18 | Variability components of standard automated perimetry and frequency-doubling technology perimetry 显示文摘 | Spry PG Johnson CA McKendrick AM | 2001 | Invest Ophthalmol Vis Sci2001，42，： | 1 |
| 19 | 24-Hour monitoring of intraocularpressure in glaucoma management:a retrospective review显示文摘 | Hughes E Spry P Diamond J | 2003 | J Glaucoma2003，12，3： | 1 |
| 20 | Effect of contrast media on mega- voltage photon beam dosimetry显示文摘 | Rankine AW Lanzon P J Spry NA | 2008 | Med Dosim2008，33，3： | 1 |
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