This pathway provides an overview of cell types, therapeutic targets, drugs, new proposed targets and pathways implicated in spinal cord injury. Spinal cord injury is a complex multistep process that involves the regulation of gene expression and signaling in motor neurons, oligodentrocytes, microglia, and astrocytes that trigger immediate immune responses lasting several weeks. Within 24 hours, chemoattractants and cytokines released from the site of injury activate neutrophils which further recruit B and T cells or recruit monocytes that ultimately result in infiltration and activation by microglia and macrophages. These immune responses result in inflammation, excitotoxicity, cell death, formation of glial scar, and suppression of axonal regeneration. An increase in the expression of cell cycle genes further results in proliferation of astrocytes and microglia that leads to apoptosis and necrosis of oligodentrocytes and neurons. An example therapy is the administration of the immunosuppressant FK506, also used in transplantation to offer neuroprotection.
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HomologyConvert
This pathway was inferred from Homo sapiens pathway WP2431(80343) with a 97.0% conversion rate.
Chalimoniuk M, King-Pospisil K, Metz CN, Toborek M; ''Macrophage migration inhibitory factor induces cell death and decreases neuronal nitric oxide expression in spinal cord neurons.''; Neuroscience, 2006 PubMedEurope PMCScholia
Lأ³pez-Vales R, Ghasemlou N, Redensek A, Kerr BJ, Barbayianni E, Antonopoulou G, Baskakis C, Rathore KI, Constantinou-Kokotou V, Stephens D, Shimizu T, Dennis EA, Kokotos G, David S; ''Phospholipase A2 superfamily members play divergent roles after spinal cord injury.''; FASEB J, 2011 PubMedEurope PMCScholia
Dekaban GA, Thawer S; ''Pathogenic antibodies are active participants in spinal cord injury.''; J Clin Invest, 2009 PubMedEurope PMCScholia
Huang C, Han X, Li X, Lam E, Peng W, Lou N, Torres A, Yang M, Garre JM, Tian GF, Bennett MV, Nedergaard M, Takano T; ''Critical role of connexin 43 in secondary expansion of traumatic spinal cord injury.''; J Neurosci, 2012 PubMedEurope PMCScholia
Tohda C, Kuboyama T; ''Current and future therapeutic strategies for functional repair of spinal cord injury.''; Pharmacol Ther, 2011 PubMedEurope PMCScholia
Chu GK, Yu W, Fehlings MG; ''The p75 neurotrophin receptor is essential for neuronal cell survival and improvement of functional recovery after spinal cord injury.''; Neuroscience, 2007 PubMedEurope PMCScholia
Zhang S, Huan W, Wei H, Shi J, Fan J, Zhao J, Shen A, Teng H; ''FOXO3a/p27kip1 expression and essential role after acute spinal cord injury in adult rat.''; J Cell Biochem, 2013 PubMedEurope PMCScholia
David S, Kroner A; ''Repertoire of microglial and macrophage responses after spinal cord injury.''; Nat Rev Neurosci, 2011 PubMedEurope PMCScholia
Tonai T, Shiba K, Taketani Y, Ohmoto Y, Murata K, Muraguchi M, Ohsaki H, Takeda E, Nishisho T; ''A neutrophil elastase inhibitor (ONO-5046) reduces neurologic damage after spinal cord injury in rats.''; J Neurochem, 2001 PubMedEurope PMCScholia
Wang YF, Fan ZK, Cao Y, Yu DS, Zhang YQ, Wang YS; ''2-Methoxyestradiol inhibits the up-regulation of AQP4 and AQP1 expression after spinal cord injury.''; Brain Res, 2011 PubMedEurope PMCScholia
Hashimoto M, Ito T, Fukumitsu H, Nomoto H, Furukawa Y, Furukawa S; ''Stimulation of production of glial cell line-derived neurotrophic factor and nitric oxide by lipopolysaccharide with different dose-responsiveness in cultured rat macrophages.''; Biomed Res, 2005 PubMedEurope PMCScholia
Floriddia EM, Rathore KI, Tedeschi A, Quadrato G, Wuttke A, Lueckmann JM, Kigerl KA, Popovich PG, Di Giovanni S; ''''; , PubMedEurope PMCScholia
Saganovأ، K, Gأ،lik J, Blaإ،ko J, Korimovأ، A, Raؤچekovأ، E, Vanickأ½ I; ''''; , PubMedEurope PMCScholia
Pajoohesh-Ganji A, Knoblach SM, Faden AI, Byrnes KR; ''Characterization of inflammatory gene expression and galectin-3 function after spinal cord injury in mice.''; Brain Res, 2012 PubMedEurope PMCScholia
Erschbamer M, Pernold K, Olson L; ''Inhibiting epidermal growth factor receptor improves structural, locomotor, sensory, and bladder recovery from experimental spinal cord injury.''; J Neurosci, 2007 PubMedEurope PMCScholia
Pajoohesh-Ganji A, Knoblach SM, Faden AI, Byrnes KR; ''Characterization of inflammatory gene expression and galectin-3 function after spinal cord injury in mice.''; Brain Res, 2012 PubMedEurope PMCScholia
Ju P, Zhang S, Yeap Y, Feng Z; ''Induction of neuronal phenotypes from NG2+ glial progenitors by inhibiting epidermal growth factor receptor in mouse spinal cord injury.''; Glia, 2012 PubMedEurope PMCScholia
Resnick DK, Graham SH, Dixon CE, Marion DW; ''Role of cyclooxygenase 2 in acute spinal cord injury.''; J Neurotrauma, 1998 PubMedEurope PMCScholia
Genovese T, Mazzon E, Crisafulli C, Di Paola R, Muiأ C, Esposito E, Bramanti P, Cuzzocrea S; ''TNF-alpha blockage in a mouse model of SCI: evidence for improved outcome.''; Shock, 2008 PubMedEurope PMCScholia
Jain A, McKeon RJ, Brady-Kalnay SM, Bellamkonda RV; ''Sustained delivery of activated Rho GTPases and BDNF promotes axon growth in CSPG-rich regions following spinal cord injury.''; PLoS One, 2011 PubMedEurope PMCScholia
Fabes J, Anderson P, Yأ،أ±ez-Muأ±oz RJ, Thrasher A, Brennan C, Bolsover S; ''''; , PubMedEurope PMCScholia
Shim SO, Cafferty WB, Schmidt EC, Kim BG, Fujisawa H, Strittmatter SM; ''PlexinA2 limits recovery from corticospinal axotomy by mediating oligodendrocyte-derived Sema6A growth inhibition.''; Mol Cell Neurosci, 2012 PubMedEurope PMCScholia
Schwab JM, Frei E, Klusman I, Schnell L, Schwab ME, Schluesener HJ; ''AIF-1 expression defines a proliferating and alert microglial/macrophage phenotype following spinal cord injury in rats.''; J Neuroimmunol, 2001 PubMedEurope PMCScholia
Terayama R, Bando Y, Murakami K, Kato K, Kishibe M, Yoshida S; ''Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury.''; Neuroscience, 2007 PubMedEurope PMCScholia
Adjan VV, Hauser KF, Bakalkin G, Yakovleva T, Gharibyan A, Scheff SW, Knapp PE; ''Caspase-3 activity is reduced after spinal cord injury in mice lacking dynorphin: differential effects on glia and neurons.''; Neuroscience, 2007 PubMedEurope PMCScholia
Lee JK, Geoffroy CG, Chan AF, Tolentino KE, Crawford MJ, Leal MA, Kang B, Zheng B; ''''; , PubMedEurope PMCScholia
Farooque M, Isaksson J, Olsson Y; ''Improved recovery after spinal cord trauma in ICAM-1 and P-selectin knockout mice.''; Neuroreport, 1999 PubMedEurope PMCScholia
Pineau I, Sun L, Bastien D, Lacroix S; ''Astrocytes initiate inflammation in the injured mouse spinal cord by promoting the entry of neutrophils and inflammatory monocytes in an IL-1 receptor/MyD88-dependent fashion.''; Brain Behav Immun, 2010 PubMedEurope PMCScholia
DAGCI T, ARMAGAN G, KONYALIOGLU S, YALCIN A; ''Alterations in the expression of the apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/ref-1) and DNA damage in the caudal region of acute and chronic spinal cord injured rats treated by embryonic neural stem cells.''; Physiol Res, 2009 PubMedEurope PMCScholia
Saganovأ، K, Orendأ،covأ، J, Sulla I Jr, FilipcØ£Âk P, CØ£Âzkovأ، D, Vanickأ½ I; ''''; , PubMedEurope PMCScholia
Woods AS, Kaminski R, Oz M, Wang Y, Hauser K, Goody R, Wang HY, Jackson SN, Zeitz P, Zeitz KP, Zolkowska D, Schepers R, Nold M, Danielson J, Grأ¤slund A, Vukojevic V, Bakalkin G, Basbaum A, Shippenberg T; ''Decoy peptides that bind dynorphin noncovalently prevent NMDA receptor-mediated neurotoxicity.''; J Proteome Res, 2006 PubMedEurope PMCScholia
Di Giovanni S, Knoblach SM, Brandoli C, Aden SA, Hoffman EP, Faden AI; ''''; , PubMedEurope PMCScholia
Lee SM, Rosen S, Weinstein P, van Rooijen N, Noble-Haeusslein LJ; ''Prevention of both neutrophil and monocyte recruitment promotes recovery after spinal cord injury.''; J Neurotrauma, 2011 PubMedEurope PMCScholia
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