Spinal cord injury (Rattus norvegicus)

From WikiPathways

Jump to: navigation, search
3326Plxna2Ltb4rNOLTB4Cspg4Tnfsf13Tnfsf13bPdynNgfrLtbCd47Ptprz1222436427Motor NeuronOligodendrocyteAstroctyeSpinal Cord InjuryTimePro-InflammatoryFactorsZfp36Fcgr2aPrb1PtpraIl1bZfp36Nos2TnfNr4a1Il4Btg2Btg2FBRCdk2Nos1Il2TnfIl6Tlr4FosIl1bTgfb1Tlr4TnfEgr1FosMmp12IfngGlial ScarAstrocyte GliosisSwelling/EdemaMbpAntigens ReleasedRtn4C5Cxcl1Neutrophil Chemoattractants29, 34IL8NeurtrophilsMonocytesAqp410TTLegendTT:Therapeutic Target (increase)TTTTTT:Therapeutic Target (decrease)T-CellsB-CellsB Cell Stimulating5Activated Microglia/Macrophages(Transient)RepairIl1bNos2TnfArg1TOXIC FERROUSIRONFocal AdensionsEpha41, 11TTEfnb2TTTTTTTTCxcl10Neuro protectionAntibody ReleaseNeuronalInjuryResponseAstrocyteInjuryResponseG1-S Cell Cycle Re-entry (TT)23Ccng1MicrogliaMicrogliaActivationAxonal RetractionRecruitmentRecruitmentMmp9TT30Chondroitin Sulfate Proteoglycans3NcanSlit1Axon Retraction3Slit2Slit3Ntn1RgmaTTTTTTTTTTMmp930Mmp9Mmp930TT30TTTTCcr2Il1r129TTECM BreakdownECM BreakdownIl1aCxcl1Monocyte Chemoattractants29, 34Cxcl2Ccl2OligodendrocyteInjury ResponsePla2g6Pla2g5Pla2g2amelittinInflammationDemyelinationAnxa1TT12TTTTTTRed Blood CellsMyelinEndothelial LeukocyteAdehsion Factors17Icam1SelpTTTTPlasticityKlk832TTMicrogliaActivated Microglia/MacrophagesActivated Microglia/MacrophagesGfapTT30IntermediateFillament40Cdk4Tacr1E2f5Rb1PrkcaE2f1Mapk1Ccnd1MycGadd45aMapk3TTTTTTAstroctyeNeuron & OligodendrocyteApoptosis/NecrosisMicrogliaProliferationCasp3Tp53CytotoxicCytotoxicChst11VcanCol4a1Xylt1Col2a1AcanBcanGlial Scar FromationSox9Axonal GrowthInhibition40IgG, IgMTp53TT6TTTTGrin1Vim1841TTT Cell Stimulating5FK50619Ppp3caTTFK506FK5063838Gap43TTFK506Axonal Regeneration38Fkbp1aIl2C3 ToxinC1Q and Fc receptive cellsMagRtn4RhoaRhocRhobRock2OmgRtn4rLilrb331MyelinInjury ResponseArachidonic acidPGH2PTGS225TT21ROSNox4Mir23bOlomoucine15Cdk1Gdnf2TTSema6aTT24Axonal GrowthInhibitionGja1ATP-Release7TTBdnfTTImmediate Response Genes23


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 multi-step 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.

Quality Tags

Ontology Terms



View all...
  1. Puschmann TB, Turnley AM; ''Eph receptor tyrosine kinases regulate astrocyte cytoskeletal rearrangement and focal adhesion formation.''; J Neurochem, 2010 PubMed Europe PMC Scholia
  2. 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 PubMed Europe PMC Scholia
  3. Kitayama M, Ueno M, Itakura T, Yamashita T; ''Activated microglia inhibit axonal growth through RGMa.''; PLoS One, 2011 PubMed Europe PMC Scholia
  4. 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 PubMed Europe PMC Scholia
  5. Dekaban GA, Thawer S; ''Pathogenic antibodies are active participants in spinal cord injury.''; J Clin Invest, 2009 PubMed Europe PMC Scholia
  6. Floriddia EM, Rathore KI, Tedeschi A, Quadrato G, Wuttke A, Lueckmann JM, Kigerl KA, Popovich PG, Di Giovanni S; ''p53 Regulates the neuronal intrinsic and extrinsic responses affecting the recovery of motor function following spinal cord injury.''; J Neurosci, 2012 PubMed Europe PMC Scholia
  7. 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 PubMed Europe PMC Scholia
  8. Wu J, Stoica BA, Faden AI; ''Cell cycle activation and spinal cord injury.''; Neurotherapeutics, 2011 PubMed Europe PMC Scholia
  9. Lavezzi AM, Casale V, Oneda R, Weese-Mayer DE, Matturri L; ''Sudden Infant Death Syndrome and Sudden Intrauterine Unexplained Death: Correlation Between Hypoplasia of Raphe Nuclei and Serotonin Transporter Gene Promoter Polymorphism.''; Pediatr Res, 2009 PubMed Europe PMC Scholia
  10. Saadoun S, Bell BA, Verkman AS, Papadopoulos MC; ''Greatly improved neurological outcome after spinal cord compression injury in AQP4-deficient mice.''; Brain, 2008 PubMed Europe PMC Scholia
  11. Fabes J, Anderson P, Yanez-Munoz RJ, Thrasher A, Brennan C, Bolsover S; ''Accumulation of the inhibitory receptor EphA4 may prevent regeneration of corticospinal tract axons following lesion.''; Eur J Neurosci, 2006 PubMed Europe PMC Scholia
  12. Liu NK, Zhang YP, Han S, Pei J, Xu LY, Lu PH, Shields CB, Xu XM; ''Annexin A1 reduces inflammatory reaction and tissue damage through inhibition of phospholipase A2 activation in adult rats following spinal cord injury.''; J Neuropathol Exp Neurol, 2007 PubMed Europe PMC Scholia
  13. Lee JK, Geoffroy CG, Chan AF, Tolentino KE, Crawford MJ, Leal MA, Kang B, Zheng B; ''Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice.''; Neuron, 2010 PubMed Europe PMC Scholia
  14. Yu CG, Yezierski RP, Joshi A, Raza K, Li Y, Geddes JW; ''Involvement of ERK2 in traumatic spinal cord injury.''; J Neurochem, 2010 PubMed Europe PMC Scholia
  15. Tian DS, Dong Q, Pan DJ, He Y, Yu ZY, Xie MJ, Wang W; ''Attenuation of astrogliosis by suppressing of microglial proliferation with the cell cycle inhibitor olomoucine in rat spinal cord injury model.''; Brain Res, 2007 PubMed Europe PMC Scholia
  16. Ankeny DP, Guan Z, Popovich PG; ''B cells produce pathogenic antibodies and impair recovery after spinal cord injury in mice.''; J Clin Invest, 2009 PubMed Europe PMC Scholia
  17. Farooque M, Isaksson J, Olsson Y; ''Improved recovery after spinal cord trauma in ICAM-1 and P-selectin knockout mice.''; Neuroreport, 1999 PubMed Europe PMC Scholia
  18. 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, Graeslund A, Vukojevic V, Bakalkin G, Basbaum A, Shippenberg T; ''Decoy peptides that bind dynorphin noncovalently prevent NMDA receptor-mediated neurotoxicity.''; J Proteome Res, 2006 PubMed Europe PMC Scholia
  19. Saganova K, Galik J, Blasko J, Korimova A, Racekova E, Vanicky I; ''Immunosuppressant FK506: focusing on neuroprotective effects following brain and spinal cord injury.''; Life Sci, 2012 PubMed Europe PMC Scholia
  20. Sharma HS; ''Early microvascular reactions and blood-spinal cord barrier disruption are instrumental in pathophysiology of spinal cord injury and repair: novel therapeutic strategies including nanowired drug delivery to enhance neuroprotection.''; J Neural Transm, 2011 PubMed Europe PMC Scholia
  21. Im YB, Jee MK, Choi JI, Cho HT, Kwon OH, Kang SK; ''Molecular targeting of NOX4 for neuropathic pain after traumatic injury of the spinal cord.''; Cell Death Dis, 2012 PubMed Europe PMC Scholia
  22. Saiwai H, Ohkawa Y, Yamada H, Kumamaru H, Harada A, Okano H, Yokomizo T, Iwamoto Y, Okada S; ''The LTB4-BLT1 axis mediates neutrophil infiltration and secondary injury in experimental spinal cord injury.''; Am J Pathol, 2010 PubMed Europe PMC Scholia
  23. Di Giovanni S, Knoblach SM, Brandoli C, Aden SA, Hoffman EP, Faden AI; ''Gene profiling in spinal cord injury shows role of cell cycle in neuronal death.''; Ann Neurol, 2003 PubMed Europe PMC Scholia
  24. 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 PubMed Europe PMC Scholia
  25. Resnick DK, Graham SH, Dixon CE, Marion DW; ''Role of cyclooxygenase 2 in acute spinal cord injury.''; J Neurotrauma, 1998 PubMed Europe PMC Scholia
  26. Lopez-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 PubMed Europe PMC Scholia
  27. Myers SA, DeVries WH, Andres KR, Gruenthal MJ, Benton RL, Hoying JB, Hagg T, Whittemore SR; ''CD47 knockout mice exhibit improved recovery from spinal cord injury.''; Neurobiol Dis, 2011 PubMed Europe PMC Scholia
  28. Lord-Fontaine S, Yang F, Diep Q, Dergham P, Munzer S, Tremblay P, McKerracher L; '' Local inhibition of Rho signaling by cell-permeable recombinant protein BA-210 prevents secondary damage and promotes functional recovery following acute spinal cord injury.''; J Neurotrauma, 2008 PubMed Europe PMC Scholia
  29. 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 PubMed Europe PMC Scholia
  30. 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 PubMed Europe PMC Scholia
  31. Tohda C, Kuboyama T; ''Current and future therapeutic strategies for functional repair of spinal cord injury.''; Pharmacol Ther, 2011 PubMed Europe PMC Scholia
  32. 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 PubMed Europe PMC Scholia
  33. David S, Kroner A; ''Repertoire of microglial and macrophage responses after spinal cord injury.''; Nat Rev Neurosci, 2011 PubMed Europe PMC Scholia
  34. 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 PubMed Europe PMC Scholia
  35. Cafferty WB, Duffy P, Huebner E, Strittmatter SM; ''MAG and OMgp synergize with Nogo-A to restrict axonal growth and neurological recovery after spinal cord trauma.''; J Neurosci, 2010 PubMed Europe PMC Scholia
  36. 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 PubMed Europe PMC Scholia
  37. McKillop WM, Dragan M, Schedl A, Brown A; ''Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury.''; Glia, 2013 PubMed Europe PMC Scholia
  38. Saganova K, Orendacova J, Sulla I Jr, Filipci­k P, Cizkova D, Vanicky I; ''Effects of long-term FK506 administration on functional and histopathological outcome after spinal cord injury in adult rat.''; Cell Mol Neurobiol, 2009 PubMed Europe PMC Scholia
  39. Liu NK, Zhang YP, Titsworth WL, Jiang X, Han S, Lu PH, Shields CB, Xu XM; ''A novel role of phospholipase A2 in mediating spinal cord secondary injury.''; Ann Neurol, 2006 PubMed Europe PMC Scholia
  40. Eng LF, Ghirnikar RS, Lee YL; ''Glial fibrillary acidic protein: GFAP-thirty-one years (1969-2000).''; Neurochem Res, 2000 PubMed Europe PMC Scholia
  41. Menet V, Prieto M, Privat A, Gimenez y Ribotta M; ''Axonal plasticity and functional recovery after spinal cord injury in mice deficient in both glial fibrillary acidic protein and vimentin genes.''; Proc Natl Acad Sci U S A, 2003 PubMed Europe PMC Scholia


View all...
120271view12:47, 23 November 2021EgonwRemoved whitespace in the pubmed id
117015view11:25, 16 May 2021EweitzModified title
106971view13:43, 17 September 2019MaintBotHMDB identifier normalization
87680view08:55, 25 July 2016LindarieswijkOntology Term : 'disease pathway' added !
83002view05:04, 17 November 2015Mkutmonremoved redundant refrence
83001view05:01, 17 November 2015Mkutmonfixed errors in references
83000view04:40, 17 November 2015Mkutmonfix outdated identifiers
81936view00:13, 6 September 2015AlexanderPicoNo rat homolog for IL8; removed human xref
79923view11:26, 27 April 2015EveloFixed homolog issue for C5
79916view11:01, 27 April 2015EveloCorrected datasource for ENSG00000106804 (was gene cards should have been ENSEMBL), still needs replaced by rat homologe
78470view10:27, 7 January 2015MaintBotadded missing graphIds
71102view17:16, 4 October 2013DMicaelModified description
69987view22:02, 11 July 2013MaintBotupdated to 2013 schema
58948view18:14, 21 February 2013MaintBotUpdated Ensembl data source
57152view12:40, 23 January 2013EgonwUsed "PubChem-compound"
55949view23:18, 28 December 2012NsalomonisOntology Term : 'traumatic neurosis' added !
55948view23:17, 28 December 2012NsalomonisOntology Term : 'spinal cord disease' added !
55947view23:17, 28 December 2012NsalomonisOntology Term : 'astrocyte of the spinal cord' added !
55946view23:15, 28 December 2012NsalomonisNew pathway

External references


View all...
NameTypeDatabase referenceComment
AcanGeneProductENSRNOG00000028992 (Ensembl)
Anxa1GeneProductENSRNOG00000017469 (Ensembl)
Aqp4GeneProductENSRNOG00000016043 (Ensembl)
Arachidonic acidMetaboliteHMDB0001043 (HMDB)
Arg1GeneProductENSRNOG00000013304 (Ensembl)
BcanGeneProductENSRNOG00000018798 (Ensembl)
BdnfGeneProduct24225 (Entrez Gene)
Btg2GeneProductENSRNOG00000003300 (Ensembl)
C5GeneProductENSRNOG00000018899 (Ensembl)
Casp3GeneProductENSRNOG00000010475 (Ensembl)
Ccl2GeneProductENSRNOG00000007159 (Ensembl)
Ccnd1GeneProductENSRNOG00000020918 (Ensembl)
Ccng1GeneProductENSRNOG00000003256 (Ensembl)
Ccr2GeneProductENSRNOG00000006755 (Ensembl)
Cd47GeneProductENSRNOG00000001964 (Ensembl)
Cdk1GeneProductENSRNOG00000000632 (Ensembl)
Cdk2GeneProductENSRNOG00000006469 (Ensembl)
Cdk4GeneProductENSRNOG00000025602 (Ensembl)
Chst11GeneProductENSRNOG00000008885 (Ensembl)
Col2a1GeneProductENSRNOG00000058560 (Ensembl)
Col4a1GeneProductENSRNOG00000016281 (Ensembl)
Cspg4GeneProductENSRNOG00000017208 (Ensembl)
Cxcl10GeneProductENSRNOG00000022256 (Ensembl)
Cxcl1GeneProductENSRNOG00000002802 (Ensembl)
Cxcl2GeneProductENSRNOG00000002792 (Ensembl)
E2f1GeneProductENSRNOG00000016708 (Ensembl)
E2f5GeneProductENSRNOG00000010760 (Ensembl)
Efnb2GeneProductENSRNOG00000014648 (Ensembl)
Egr1GeneProductENSRNOG00000019422 (Ensembl)
Epha4GeneProductENSRNOG00000013213 (Ensembl)
FK506Metabolite104987-11-3 (CAS)
Fcgr2aGeneProductENSRNOG00000049422 (Ensembl)
Fkbp1aGeneProductENSRNOG00000008822 (Ensembl)
FosGeneProductENSRNOG00000008015 (Ensembl)
Gadd45aGeneProductENSRNOG00000005615 (Ensembl)
Gap43GeneProductENSRNOG00000001528 (Ensembl)
GdnfGeneProductENSRNOG00000012819 (Ensembl)
GfapGeneProductENSRNOG00000002919 (Ensembl)
Gja1GeneProductENSRNOG00000000805 (Ensembl)
Grin1GeneProductENSRNOG00000011726 (Ensembl)
Icam1GeneProductENSRNOG00000020679 (Ensembl)
IfngGeneProductENSRNOG00000007468 (Ensembl)
Il1aGeneProductENSRNOG00000004575 (Ensembl)
Il1bGeneProductENSRNOG00000004649 (Ensembl)
Il1r1GeneProductENSRNOG00000014504 (Ensembl)
Il2GeneProductENSRNOG00000017348 (Ensembl)
Il4GeneProductENSRNOG00000007624 (Ensembl)
Il6GeneProductENSRNOG00000010278 (Ensembl)
Klk8GeneProductENSRNOG00000018580 (Ensembl)
LTB4Metabolite169 (PubChem-compound)
Lilrb3GeneProductENSRNOG00000054954 (Ensembl)
Ltb4rGeneProductENSRNOG00000020399 (Ensembl)
LtbGeneProductENSRNOG00000000836 (Ensembl)
MagGeneProductENSRNOG00000021023 (Ensembl)
Mapk1GeneProductENSRNOG00000001849 (Ensembl)
Mapk3GeneProductENSRNOG00000053583 (Ensembl)
MbpGeneProductENSRNOG00000016516 (Ensembl)
Mir23bGeneProduct100314002 (Entrez Gene)
Mmp12GeneProductENSRNOG00000030187 (Ensembl)
Mmp9GeneProductENSRNOG00000017539 (Ensembl)
MycGeneProductENSRNOG00000004500 (Ensembl)
NOMetabolite145068 (PubChem-compound)
NcanGeneProductENSRNOG00000048036 (Ensembl)
NgfrGeneProductENSRNOG00000005392 (Ensembl)
Nos1GeneProductENSRNOG00000001130 (Ensembl)
Nos2GeneProductENSRNOG00000057443 (Ensembl)
Nox4GeneProductENSRNOG00000013925 (Ensembl)
Nr4a1GeneProductENSRNOG00000007607 (Ensembl)
Ntn1GeneProductENSRNOG00000003947 (Ensembl)
OlomoucineMetaboliteHMDB0035233 (HMDB)
OmgGeneProductENSRNOG00000014107 (Ensembl)
PGH2MetaboliteHMDB0001381 (HMDB)
PTGS2GeneProduct469616 (Entrez Gene)
PdynGeneProductENSRNOG00000026036 (Ensembl)
Pla2g2aGeneProductENSRNOG00000016945 (Ensembl)
Pla2g5GeneProductENSRNOG00000016838 (Ensembl)
Pla2g6GeneProductENSRNOG00000012295 (Ensembl)
Plxna2GeneProductENSRNOG00000007324 (Ensembl)
Ppp3caGeneProductENSRNOG00000009882 (Ensembl)
Prb1GeneProductENSRNOG00000010485 (Ensembl)
PrkcaGeneProductENSRNOG00000003491 (Ensembl)
PtpraGeneProductENSRNOG00000021223 (Ensembl)
Ptprz1GeneProductENSRNOG00000006030 (Ensembl)
Rb1GeneProductENSRNOG00000016029 (Ensembl)
RgmaGeneProductENSRNOG00000012874 (Ensembl)
RhoaGeneProductENSRNOG00000050519 (Ensembl)
RhobGeneProductENSRNOG00000021403 (Ensembl)
RhocGeneProductENSRNOG00000012630 (Ensembl)
Rock2GeneProductENSRNOG00000004496 (Ensembl)
Rtn4GeneProductENSRNOG00000004621 (Ensembl)
Rtn4rGeneProductENSRNOG00000030920 (Ensembl)
SelpGeneProductENSRNOG00000002794 (Ensembl)
Sema6aGeneProduct361324 (Entrez Gene)
Slit1GeneProductENSRNOG00000026065 (Ensembl)
Slit2GeneProductENSRNOG00000003840 (Ensembl)
Slit3GeneProductENSRNOG00000007377 (Ensembl)
Sox9GeneProduct140586 (Entrez Gene)
Tacr1GeneProductENSRNOG00000005853 (Ensembl)
Tgfb1GeneProductENSRNOG00000020652 (Ensembl)
Tlr4GeneProductENSRNOG00000010522 (Ensembl)
TnfGeneProductENSRNOG00000000837 (Ensembl)
Tnfsf13GeneProductENSRNOG00000014171 (Ensembl)
Tnfsf13bGeneProductENSRNOG00000014464 (Ensembl)
Tp53GeneProductENSRNOG00000010756 (Ensembl)
VcanGeneProductENSRNOG00000029212 (Ensembl)
VimGeneProductENSRNOG00000018087 (Ensembl)
Xylt1GeneProductENSRNOG00000056658 (Ensembl)
Zfp36GeneProductENSRNOG00000058388 (Ensembl)
melittinMetabolite16133648 (PubChem-compound)

Annotated Interactions

No annotated interactions

Personal tools