RT Journal Article SR Electronic T1 Minocycline Alleviates Death of Oligodendrocytes by Inhibiting Pro-Nerve Growth Factor Production in Microglia after Spinal Cord Injury JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 7751 OP 7761 DO 10.1523/JNEUROSCI.1661-07.2007 VO 27 IS 29 A1 Tae Y. Yune A1 Jee Y. Lee A1 Gil Y. Jung A1 Sun J. Kim A1 Mei H. Jiang A1 Young C. Kim A1 Young J. Oh A1 George J. Markelonis A1 Tae H. Oh YR 2007 UL http://www.jneurosci.org/content/27/29/7751.abstract AB Spinal cord injury (SCI) causes a permanent neurological disability, and no satisfactory treatment is currently available. After SCI, pro-nerve growth factor (proNGF) is known to play a pivotal role in apoptosis of oligodendrocytes, but the cell types producing proNGF and the signaling pathways involved in proNGF production are primarily unknown. Here, we show that minocycline improves functional recovery after SCI in part by reducing apoptosis of oligodendrocytes via inhibition of proNGF production in microglia. After SCI, the stress-responsive p38 mitogen-activated protein kinase (p38MAPK) was activated only in microglia, and proNGF was produced by microglia via the p38MAPK-mediated pathway. Minocycline treatment significantly reduced proNGF production in microglia in vitro and in vivo by inhibition of the phosphorylation of p38MAPK. Furthermore, minocycline treatment inhibited p75 neurotrophin receptor expression and RhoA activation after injury. Finally, minocycline treatment inhibited oligodendrocyte death and improved functional recovery after SCI. These results suggest that minocycline may represent a potential therapeutic agent for acute SCI in humans.