The role of propriospinal interneurons in recovery from spinal cord injury

Over one hundred years ago, Sir Charles Sherrington described a population of spinal cord interneurons (INs) that connect multiple spinal cord segments and participate in complex or 'long' motor reflexes. These neurons were subsequently termed propriospinal neurons (PNs) and are known to play a crucial role in motor control and sensory processing. Recent work has shown that PNs may also be an important substrate for recovery from spinal cord injury (SCI) as they contribute to plastic reorganisation of spinal circuits. The location, inter-segmental projection pattern and sheer number of PNs mean that after SCI, a significant number of them are capable of 'bridging' an incomplete spinal cord lesion. When these properties are combined with the capacity of PNs to activate and coordinate locomotor central pattern generators (CPGs), it is clear they are ideally placed to assist locomotor recovery. Here we summarise the anatomy, organisation and function of PNs in the uninjured spinal cord, briefly outline the pathophysiology of SCI, describe how PNs contribute to recovery of motor function, and finally, we discuss the mechanisms that underlie PN plasticity. We propose there are two major challenges for PN research. The first is to learn more about ways we can promote PN plasticity and manipulate the 'hostile' micro-environment that limits regeneration in the damaged spinal cord. The second is to study the cellular/intrinsic properties of PNs to better understand their function in both the normal and injured spinal cord. This article is part of a Special Issue entitled 'Synaptic Plasticity & Interneurons'.

[1]  P. Caroni,et al.  New EMBO members' review: actin cytoskeleton regulation through modulation of PI(4,5)P(2) rafts. , 2001, The EMBO journal.

[2]  D. Stelzner,et al.  Chapter 12 – The Propriospinal System , 2009 .

[3]  J. Silver,et al.  Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[4]  J. Guest,et al.  The Ability of Human Schwann Cell Grafts to Promote Regeneration in the Transected Nude Rat Spinal Cord , 1997, Experimental Neurology.

[5]  R. Kearney,et al.  Reflex response of human arm muscles to cutaneous stimulation of the foot , 1979, Brain Research.

[6]  J. Goldman,et al.  Endogenous Progenitors Remyelinate Demyelinated Axons in the Adult CNS , 1997, Neuron.

[7]  J. Broton,et al.  Interlimb reflex activity after spinal cord injury in man: strengthening response patterns are consistent with ongoing synaptic plasticity , 2005, Clinical Neurophysiology.

[8]  D. Vasilenko Propriospinal pathways in the ventral funicles of the cat spinal cord: their effects on lumbosacral motoneurones , 1975, Brain Research.

[9]  K. Fouad,et al.  Cervical sprouting of corticospinal fibers after thoracic spinal cord injury accompanies shifts in evoked motor responses , 2001, Current Biology.

[10]  S. Sasaki,et al.  Dexterous finger movements in primate without monosynaptic corticomotoneuronal excitation. , 2004, Journal of neurophysiology.

[11]  P. Nathan,et al.  Fasciculi proprii of the spinal cord in man. , 1959, Brain : a journal of neurology.

[12]  Y. Hosoya,et al.  The location of spinal neurons with long descending axons (long descending propriospinal tract neurons) in the cat: A study with the horseradish peroxidase technique , 1979, The Journal of comparative neurology.

[13]  N. Hirokawa,et al.  Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport. , 2000, Science.

[14]  R. Bellamkonda,et al.  Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury , 2009, Proceedings of the National Academy of Sciences.

[15]  W. Tetzlaff,et al.  Promoting axonal regeneration in the central nervous system by enhancing the cell body response to axotomy , 2002, Journal of neuroscience research.

[16]  P. Caroni New EMBO members' review: actin cytoskeleton regulation through modulation of PI(4,5)P(2) rafts. , 2001, The EMBO journal.

[17]  Mary P Galea,et al.  Axonal Regeneration and Lack of Astrocytic Gliosis in EphA4-Deficient Mice , 2004, The Journal of Neuroscience.

[18]  A. Aguayo,et al.  Axons from CNS neurones regenerate into PNS grafts , 1980, Nature.

[19]  B. Alstermark,et al.  Lack of monosynaptic corticomotoneuronal EPSPs in rats: disynaptic EPSPs mediated via reticulospinal neurons and polysynaptic EPSPs via segmental interneurons. , 2004, Journal of neurophysiology.

[20]  M. Selzer Mechanisms of functional recovery and regeneration after spinal cord transection in larval sea lamprey. , 1978, The Journal of physiology.

[21]  P Sterling,et al.  Anatomical organization of the brachial spinal cord of the cat. 3. The propriospinal connections. , 1968, Brain research.

[22]  John Simmers,et al.  Propriospinal Circuitry Underlying Interlimb Coordination in Mammalian Quadrupedal Locomotion , 2005, The Journal of Neuroscience.

[23]  Martin E. Schwab,et al.  Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1 , 2000, Nature.

[24]  Tadashi Isa,et al.  Premotoneuronal and direct corticomotoneuronal control in the cat and macaque monkey. , 2002, Advances in experimental medicine and biology.

[25]  M. Oudega,et al.  Schwann Cell But Not Olfactory Ensheathing Glia Transplants Improve Hindlimb Locomotor Performance in the Moderately Contused Adult Rat Thoracic Spinal Cord , 2002, The Journal of Neuroscience.

[26]  J. Broton,et al.  Central nervous system plasticity after spinal cord injury in man: interlimb reflexes and the influence of cutaneous stimulation. , 1996, Electroencephalography and clinical neurophysiology.

[27]  Sergiy Yakovenko,et al.  Intraspinal stimulation caudal to spinal cord transections in rats. Testing the propriospinal hypothesis. , 2007, Journal of neurophysiology.

[28]  R. Skinner,et al.  Responses of long descending propriospinal neurons to natural and electrical types of stimuli in cat , 1980, Brain Research.

[29]  S. Sasaki,et al.  The C3–C4 propriospinal system in the cat and monkey: a spinal pre‐motoneuronal centre for voluntary motor control , 2007, Acta physiologica.

[30]  J. Fawcett,et al.  Extrinsic and intrinsic factors controlling axonal regeneration after spinal cord injury , 2009, Expert Reviews in Molecular Medicine.

[31]  S. Rossignol,et al.  Locomotor performance and adaptation after partial or complete spinal cord lesions in the cat. , 1999, Progress in brain research.

[32]  S. Miller,et al.  Coordination of movements of the hindlimbs and forelimbs in different forms of locomotion in normal and decerebrate cats , 1975, Brain Research.

[33]  J. Houlé Demonstration of the potential for chronically injured neurons to regenerate axons into intraspinal peripheral nerve grafts , 1991, Experimental Neurology.

[34]  E. E. Laslett,et al.  Note upon descending intrinsic spinal tracts in the mammalian cord , 1903, Proceedings of the Royal Society of London.

[35]  S. Di Giovanni,et al.  Molecular targets for axon regeneration: focus on the intrinsic pathways , 2009, Expert opinion on therapeutic targets.

[36]  J. Sprague A study of motor cell localization in the spinal cord of the rhesus monkey. , 1948, The American journal of anatomy.

[37]  B. Alstermark,et al.  Transneuronal transport of wheat germ agglutinin conjugated horseradish peroxidase into last order spinal interneurones projecting to acromio- and spinodeltoideus motoneurones in the cat , 1990, Experimental Brain Research.

[38]  D. Menétrey,et al.  Propriospinal fibers reaching the lumbar enlargement in the rat , 1985, Neuroscience Letters.

[39]  B. Alstermark,et al.  Pyramidal excitation in long propriospinal neurones in the cervical segments of the cat , 2004, Experimental Brain Research.

[40]  D. Stelzner,et al.  Loss of propriospinal neurons after spinal contusion injury as assessed by retrograde labeling , 2010, Neuroscience.

[41]  R. Lemon,et al.  Interspecies comparisons for the C3-C4 propriospinal system: unresolved issues. , 2002, Advances in experimental medicine and biology.

[42]  G. W. Hiebert,et al.  BDNF promotes connections of corticospinal neurons onto spared descending interneurons in spinal cord injured rats. , 2006, Brain : a journal of neurology.

[43]  L. Parada,et al.  Ephrin-B3 is a myelin-based inhibitor of neurite outgrowth. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[44]  F. Walsh,et al.  Neurite Outgrowth Stimulated by Neural Cell Adhesion Molecules Requires Growth-Associated Protein-43 (GAP-43) Function and Is Associated with GAP-43 Phosphorylation in Growth Cones , 1998, The Journal of Neuroscience.

[45]  M. Hediger,et al.  A Novel System A Isoform Mediating Na+/Neutral Amino Acid Cotransport* , 2000, The Journal of Biological Chemistry.

[46]  F. Middleton,et al.  Long descending cervical propriospinal neurons differ from thoracic propriospinal neurons in response to low thoracic spinal injury , 2010, BMC Neuroscience.

[47]  O. Kiehn,et al.  Phenotype of V2‐derived interneurons and their relationship to the axon guidance molecule EphA4 in the developing mouse spinal cord , 2007, The European journal of neuroscience.

[48]  G Colombo,et al.  Locomotor pattern in paraplegic patients: training effects and recovery of spinal cord function , 1998, Spinal Cord.

[49]  A. Markus,et al.  Neurotrophic factors and axonal growth , 2002, Current Opinion in Neurobiology.

[50]  M. Goulding,et al.  Engrailed-1 and netrin-1 regulate axon pathfinding by association interneurons that project to motor neurons. , 1999, Development.

[51]  R. Lemon,et al.  Does a C3‐C4 propriospinal system transmit corticospinal excitation in the primate? An investigation in the macaque monkey , 1998, The Journal of physiology.

[52]  H. Kuypers,et al.  Propriospinal fibers interconnecting the spinal enlargements in the cat. , 1969, Brain research.

[53]  V. Dietz Do human bipeds use quadrupedal coordination? , 2002, Trends in Neurosciences.

[54]  Keith K. Fenrich,et al.  Spinal Interneuron Axons Spontaneously Regenerate after Spinal Cord Injury in the Adult Feline , 2009, The Journal of Neuroscience.

[55]  J. Steeves,et al.  Brain‐derived neurotrophic factor applied to the motor cortex promotes sprouting of corticospinal fibers but not regeneration into a peripheral nerve transplant , 2002, Journal of neuroscience research.

[56]  C. Meehan,et al.  Axonal regeneration and development of de novo axons from distal dendrites of adult feline commissural interneurons after a proximal axotomy , 2007, The Journal of comparative neurology.

[57]  A. Cameron,et al.  Plasticity of lumbosacral propriospinal neurons is associated with the development of autonomic dysreflexia after thoracic spinal cord transection , 2008, The Journal of comparative neurology.

[58]  E. Pierrot-Deseilligny,et al.  Role of spinal premotoneurones in mediating corticospinal input to forearm motoneurones in man , 1998, The Journal of physiology.

[59]  Volker Dietz,et al.  Human Bipeds Use Quadrupedal Coordination during Locomotion , 2009, Annals of the New York Academy of Sciences.

[60]  B. Schmidt,et al.  Propriospinal neurons contribute to bulbospinal transmission of the locomotor command signal in the neonatal rat spinal cord , 2006, The Journal of physiology.

[61]  A. Lundberg,et al.  Integration in descending motor pathways controlling the forelimb in the cat , 1977, Experimental Brain Research.

[62]  Michael G Fehlings,et al.  Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. , 2008, Neurosurgical focus.

[63]  C. M. Bastiaanse,et al.  Neuronal coordination of arm and leg movements during human locomotion , 2001, The European journal of neuroscience.

[64]  E. Sybirska,et al.  Integration in descending motor pathways controlling the forelimb in the cat , 2004, Experimental Brain Research.

[65]  P. Caroni,et al.  The motility-associated proteins GAP-43, MARCKS, and CAP-23 share unique targeting and surface activity-inducing properties. , 1997, Experimental cell research.

[66]  Projection from excitatory C3–C4 propriospinal neurones to spinocerebellar and spinoreticular neurones in the C6-Th1 segments of the cat , 1990, Neuroscience Research.

[67]  Roland R Roy,et al.  Rehabilitative therapies after spinal cord injury. , 2006, Journal of neurotrauma.

[68]  H. Burton,et al.  Descending projections from the marginal cell layer and other regions of the monkey spinal cord , 1976, Brain Research.

[69]  R. Callister,et al.  Early History of Glycine Receptor Biology in Mammalian Spinal Cord Circuits , 2010, Front. Mol. Neurosci..

[70]  E. Pierrot-Deseilligny,et al.  Transmission of the cortical command for human voluntary movement through cervical propriospinal premotoneurons , 1996, Progress in Neurobiology.

[71]  Jeffrey L Goldberg,et al.  Amacrine-Signaled Loss of Intrinsic Axon Growth Ability by Retinal Ganglion Cells , 2002, Science.

[72]  B. Alstermark,et al.  Effect of spinal cord lesions on forelimb target-reaching and on visually guided switching of target-reaching in the cat , 1997, Neuroscience Research.

[73]  G. Romanes,et al.  The motor cell columns of the lumbo‐sacral spinal cord of the cat , 1951, The Journal of comparative neurology.

[74]  Zhigang He,et al.  Neuronal intrinsic barriers for axon regeneration in the adult CNS , 2010, Current Opinion in Neurobiology.

[75]  A. Blesch,et al.  Axonal responses to cellularly delivered NT-4/5 after spinal cord injury , 2004, Molecular and Cellular Neuroscience.

[76]  M. Galea,et al.  Treadmill training after spinal cord hemisection in mice promotes axonal sprouting and synapse formation and improves motor recovery. , 2008, Journal of neurotrauma.

[77]  P J Delwaide,et al.  Effects of postural changes of the upper limb on reflex transmission in the lower limb. Cervicolumbar reflex interactions in man. , 1977, Journal of neurology, neurosurgery, and psychiatry.

[78]  A. Lundberg,et al.  Integration in descending motor pathways controlling the forelimb in the cat , 2004, Experimental Brain Research.

[79]  M. Matsushita The axonal pathways of spinal neurons in the cat , 1970, The Journal of comparative neurology.

[80]  R. Foreman Integration of viscerosomatic sensory input at the spinal level. , 2000, Progress in brain research.

[81]  D. P. Lloyd,et al.  Analysis of forelimb-hindlimb reflex activity in acutely decapitate cats. , 1948, Journal of neurophysiology.

[82]  D. Morin,et al.  Forelimb locomotor generators and quadrupedal locomotion in the neonatal rat , 2001, The European journal of neuroscience.

[83]  R. Lemon,et al.  Investigation into non-monosynaptic corticospinal excitation of macaque upper limb single motor units. , 2001, Journal of neurophysiology.

[84]  B. Alstermark,et al.  Disynaptic pyramidal excitation in forelimb motoneurons mediated via C(3)-C(4) propriospinal neurons in the Macaca fuscata. , 1999, Journal of neurophysiology.

[85]  P. Kirkwood,et al.  Electrophysiological and morphological characterization of propriospinal interneurons in the thoracic spinal cord. , 2011, Journal of neurophysiology.

[86]  M. Tuszynski,et al.  Cellular GDNF delivery promotes growth of motor and dorsal column sensory axons after partial and complete spinal cord transections and induces remyelination , 2003, The Journal of comparative neurology.

[87]  S. Miller,et al.  Interlimb co-ordination in stepping in the cat. , 1973, The Journal of physiology.

[88]  B. Alstermark,et al.  In vivo recordings of bulbospinal excitation in adult mouse forelimb motoneurons. , 2004, Journal of neurophysiology.

[89]  S. Mori,et al.  Lumbar commissural interneurons with reticulospinal inputs in the cat: Morphology and discharge patterns during fictive locomotion , 2004, The Journal of comparative neurology.

[90]  Alan R. Johnson,et al.  REGENERATION IN THE VERTEBRATE CENTRAL NERVOUS SYSTEM: PHYLOGENY, ONTOGENY, AND MECHANISMS , 1995, Biological reviews of the Cambridge Philosophical Society.

[91]  Edwin Clarke,et al.  Cajal's Degeneration and regeneration of the nervous system , 1992, Medical History.

[92]  Qin He,et al.  Regulation of GAP-43 at serine 41 acts as a switch to modulate both intrinsic and extrinsic behaviors of growing neurons, via altered membrane distribution , 2009, Molecular and Cellular Neuroscience.

[93]  B. Alstermark,et al.  Properties of propriospinal neurons in the C3-C4 segments mediating disynaptic pyramidal excitation to forelimb motoneurons in the macaque monkey. , 2006, Journal of neurophysiology.

[94]  B. Cubelos,et al.  Immunohistochemical localization of the amino acid transporter SNAT2 in the rat brain , 2005, Neuroscience.

[95]  A. Tessler,et al.  Spinal shock revisited: a four-phase model , 2004, Spinal Cord.

[96]  H. Kuypers,et al.  Cells of origin of propriospinal fibers and of fibers ascending to supraspinal levels. A HRP study in cat and rhesus monkey , 1978, Brain Research.

[97]  S. Sasaki,et al.  Integration in descending motor pathways controlling the forelimb in the cat , 2004, Experimental Brain Research.

[98]  G. Terenghi,et al.  Peripheral nerve regeneration and neurotrophic factors , 1999, Journal of anatomy.

[99]  A. Aguayo,et al.  Axonal elongation into peripheral nervous system "bridges" after central nervous system injury in adult rats. , 1981, Science.

[100]  G. Raivich,et al.  The making of successful axonal regeneration: Genes, molecules and signal transduction pathways , 2007, Brain Research Reviews.

[101]  N. Kleitman,et al.  Axonal regeneration into Schwann cell‐seeded guidance channels grafted into transected adult rat spinal cord , 1995, The Journal of comparative neurology.

[102]  M. Schwab,et al.  Degeneration and regeneration of axons in the lesioned spinal cord. , 1996, Physiological reviews.

[103]  E. Schomburg,et al.  Functional organization of the spinal reflex pathways from forelimb afferents to hindlimb motoneurones in the cat , 1978, Brain Research.

[104]  M. Tuszynski,et al.  Spontaneous corticospinal axonal plasticity and functional recovery after adult central nervous system injury , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[105]  E. Sybirska,et al.  Integration in descending motor pathways controlling the forelimb in the cat , 2004, Experimental Brain Research.

[106]  James W. Rowland,et al.  Protection and repair of the injured spinal cord: a review of completed, ongoing, and planned clinical trials for acute spinal cord injury. , 2008, Neurosurgical focus.

[107]  E. Garcia-Rill,et al.  Ascending projections of long descending propriospinal tract (LDPT) neurons , 1989, Brain Research Bulletin.

[108]  J. Ditunno,et al.  Recovery of ambulation in motor-incomplete tetraplegia. , 1997, Archives of physical medicine and rehabilitation.

[109]  W. Snider,et al.  Intracellular control of developmental and regenerative axon growth , 2006, Philosophical Transactions of the Royal Society B: Biological Sciences.

[110]  David Burke,et al.  The Circuitry of the Human Spinal Cord: Propriospinal relay for descending motor commands , 2005 .

[111]  Zhigang He,et al.  Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth , 2002, Nature.

[112]  J. Szentágothai Neuronal and synaptic arrangement in the substantia gelatinosa rolandi , 1964, The Journal of comparative neurology.

[113]  G W Plant,et al.  Long-Distance Axonal Regeneration in the Transected Adult Rat Spinal Cord Is Promoted by Olfactory Ensheathing Glia Transplants , 1998, The Journal of Neuroscience.

[114]  Andrés Hurtado,et al.  Transgenic inhibition of astroglial NF‐κB leads to increased axonal sparing and sprouting following spinal cord injury , 2009, Journal of neurochemistry.

[115]  T. Südhof,et al.  A Tripartite Protein Complex with the Potential to Couple Synaptic Vesicle Exocytosis to Cell Adhesion in Brain , 1998, Cell.

[116]  O. Steward,et al.  Ascending sensory, but not other long‐tract axons, regenerate into the connective tissue matrix that forms at the site of a spinal cord injury in mice , 2003, The Journal of comparative neurology.

[117]  R. Lemon,et al.  Striking differences in transmission of corticospinal excitation to upper limb motoneurons in two primate species. , 2000, Journal of neurophysiology.

[118]  B. Calancie Interlimb reflexes following cervical spinal cord injury in man , 2004, Experimental Brain Research.

[119]  A. Lundberg,et al.  Collateral connections to the lateral reticular nucleus from cervical propriospinal neurones projecting to forelimb motoneurones in the cat , 1978, Neuroscience Letters.

[120]  R. Skinner,et al.  Cells of origin of long descending propriospinal fibers connecting the spinal enlargements in cat and monkey determined by horseradish peroxidase and electrophysiological techniques , 1979, The Journal of comparative neurology.

[121]  Martin E. Schwab,et al.  Plasticity of motor systems after incomplete spinal cord injury , 2001, Nature Reviews Neuroscience.

[122]  W. Blakemore,et al.  Locomotor deficits induced by experimental spinal cord demyelination are abolished by spontaneous remyelination. , 1997, Brain : a journal of neurology.

[123]  P. Aebischer,et al.  A Combination of BDNF and NT-3 Promotes Supraspinal Axonal Regeneration into Schwann Cell Grafts in Adult Rat Thoracic Spinal Cord , 1995, Experimental Neurology.

[124]  G. Wolstenholme,et al.  The Spinal cord , 1953 .

[125]  W. Tetzlaff,et al.  Influence of the axotomy to cell body distance in rat rubrospinal and spinal motoneurons: Differential regulation of GAP‐43, tubulins, and neurofilament‐M , 1999, The Journal of comparative neurology.

[126]  D. Stelzner,et al.  Intrinsic response of thoracic propriospinal neurons to axotomy , 2010, BMC Neuroscience.

[127]  Bingbing Song,et al.  Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury , 2008, Nature Medicine.

[128]  B. Schmidt,et al.  Propriospinal neurons are sufficient for bulbospinal transmission of the locomotor command signal in the neonatal rat spinal cord , 2008, The Journal of physiology.

[129]  R. Yezierski,et al.  Cells of origin of propriospinal connections to cat lumbosacral gray as determined with horseradish peroxidase , 1980, Experimental Neurology.

[130]  M. Antal,et al.  Propriospinal afferent and efferent connections of the lateral and medial areas of the dorsal horn (laminae I‐IV) in the rat lumbar spinal cord , 2000, The Journal of comparative neurology.

[131]  T. Ueyama,et al.  Ventral motor nucleus of the cervical enlargement in some mammals; its specific afferents from the lower cord levels and cytoarchitecture , 1973, The Journal of comparative neurology.

[132]  M. Mason,et al.  Corticospinal neurons up‐regulate a range of growth‐associated genes following intracortical, but not spinal, axotomy , 2003, The European journal of neuroscience.

[133]  Romeo Chua,et al.  Human interlimb reflexes evoked by electrical stimulation of cutaneous nerves innervating the hand and foot , 2001, Experimental Brain Research.

[134]  B. Schmidt,et al.  Propriospinal transmission of the locomotor command signal in the neonatal rat , 2010, Annals of the New York Academy of Sciences.

[135]  A. Lundberg,et al.  Integration in descending motor pathways controlling the forelimb in the cat , 1978, Experimental Brain Research.

[136]  E. Jankowska Interneuronal relay in spinal pathways from proprioceptors , 1992, Progress in Neurobiology.

[137]  C. Jaillard,et al.  The Transmembrane Semaphorin Sema4D/CD100, an Inhibitor of Axonal Growth, Is Expressed on Oligodendrocytes and Upregulated after CNS Lesion , 2003, The Journal of Neuroscience.

[138]  Xiao-Ming Xu,et al.  Glial cell line-derived neurotrophic factor-enriched bridging transplants promote propriospinal axonal regeneration and enhance myelination after spinal cord injury , 2003, Experimental Neurology.

[139]  R. Callister,et al.  An in vivo mouse spinal cord preparation for patch-clamp analysis of nociceptive processing , 2004, Journal of Neuroscience Methods.

[140]  Aqing Chen,et al.  Bridging Schwann cell transplants promote axonal regeneration from both the rostral and caudal stumps of transected adult rat spinal cord , 1997, Journal of neurocytology.

[141]  Frank Bradke,et al.  Netrin-1 Is a Novel Myelin-Associated Inhibitor to Axon Growth , 2008, The Journal of Neuroscience.

[142]  C S Sherrington,et al.  Observations on some spinal reflexes and the interconnection of spinal segments , 1903, The Journal of physiology.

[143]  L. Mckerracher,et al.  Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth , 1994, Neuron.

[144]  D. Stuart,et al.  Propriospinal control of last order interneurones of spinal reflex pathways in the cat. , 1973, Brain research.

[145]  S. Whittemore,et al.  Transplantation of Ciliary Neurotrophic Factor-Expressing Adult Oligodendrocyte Precursor Cells Promotes Remyelination and Functional Recovery after SpinalCord Injury , 2010, The Journal of Neuroscience.

[146]  A. Lozano,et al.  Expression of the growth-associated protein GAP-43 in adult rat retinal ganglion cells following axon injury , 1991, Neuron.

[147]  羽田 克彦 RGMa inhibition promotes axonal growth and recovery after spinal cord injury , 2006 .

[148]  E. Pierrot-Deseilligny,et al.  Pattern of propriospinal‐like excitation to different species of human upper limb motoneurones. , 1991, The Journal of physiology.

[149]  S. Miller,et al.  Functional organization of long ascending propriospinal pathways linking lumbo-sacral and cervical segments in the cat. , 1973, Brain research.

[150]  J. Jane,et al.  AN INVESTIGATION CONCERNING THE RESTITUTION OF MOTOR FUNCTION FOLLOWING INJURY TO THE SPINAL CORD. , 1964, Journal of neurosurgery.

[151]  Markus Rudin,et al.  Functional and Anatomical Reorganization of the Sensory-Motor Cortex after Incomplete Spinal Cord Injury in Adult Rats , 2009, The Journal of Neuroscience.

[152]  D. Stelzner,et al.  Differential vulnerability of propriospinal tract neurons to spinal cord contusion injury , 2004, The Journal of comparative neurology.

[153]  J. Nielsen,et al.  Intrinsic properties of mouse lumbar motoneurons revealed by intracellular recording in vivo. , 2010, Journal of neurophysiology.

[154]  R. Kearney,et al.  Interlimb reflexes evoked in human arm muscles by ankle displacement. , 1981, Electroencephalography and clinical neurophysiology.

[155]  M. Schwab,et al.  Dissociated neurons regenerate into sciatic but not optic nerve explants in culture irrespective of neurotrophic factors , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[156]  P. Kostyuk,et al.  Spinal interneurons. , 1979, Annual review of physiology.

[157]  P. White,et al.  Overcoming biological barriers to in vivo efficacy of antisense oligonucleotides , 2009, Expert Reviews in Molecular Medicine.

[158]  S. Lipton,et al.  Excitatory amino acids as a final common pathway for neurologic disorders. , 1994, The New England journal of medicine.

[159]  H. Müller,et al.  The CNS lesion scar: new vistas on an old regeneration barrier , 1998, Cell and Tissue Research.

[160]  G. Holstege,et al.  Propiospinal projections from the ventral and lateral funiculi to the motoneurons in the lumbosacral cord of the cat. , 1971, Brain research.

[161]  D. Stuart,et al.  A long propriospinal system with direct effect on motoneurones and on interneurones in the cat lumbosacral cord , 2004, Experimental Brain Research.

[162]  D. Prince,et al.  Modulation of epileptiform activity by glutamine and system A transport in a model of post-traumatic epilepsy , 2007, Neurobiology of Disease.

[163]  Y. Sarica,et al.  Descending lumbosacral cord potentials (DLCP) evoked by stimulation of the median nerve , 1985, Brain Research.

[164]  David P. C. Lloyd,et al.  MEDIATION OF DESCENDING LONG SPINAL REFLEX ACTIVITY , 1942 .

[165]  M. Norenberg,et al.  The pathology of human spinal cord injury: defining the problems. , 2004, Journal of neurotrauma.

[166]  Volker Dietz,et al.  Behavior of spinal neurons deprived of supraspinal input , 2010, Nature Reviews Neurology.

[167]  H. Luhmann,et al.  Inhibition of collagen IV deposition promotes regeneration of injured CNS axons , 1999, The European journal of neuroscience.

[168]  M. Filbin,et al.  Neuronal Cyclic AMP Controls the Developmental Loss in Ability of Axons to Regenerate , 2001, The Journal of Neuroscience.

[169]  V. Berezin,et al.  GAP‐43 regulates NCAM‐180‐mediated neurite outgrowth , 2006, Journal of neurochemistry.

[170]  S. Sasaki,et al.  Direct and indirect cortico-motoneuronal pathways and control of hand/arm movements. , 2007, Physiology.

[171]  T. Jessell,et al.  Control of Interneuron Fate in the Developing Spinal Cord by the Progenitor Homeodomain Protein Dbx1 , 2001, Neuron.

[172]  J. Broton,et al.  Interlimb reflexes and synaptic plasticity become evident months after human spinal cord injury. , 2002, Brain : a journal of neurology.

[173]  M. Goulding Circuits controlling vertebrate locomotion: moving in a new direction , 2009, Nature Reviews Neuroscience.

[174]  Jerry Silver,et al.  Combining an Autologous Peripheral Nervous System “Bridge” and Matrix Modification by Chondroitinase Allows Robust, Functional Regeneration beyond a Hemisection Lesion of the Adult Rat Spinal Cord , 2006, The Journal of Neuroscience.

[175]  T. Branchek,et al.  Molecular heterogeneity of the gamma-aminobutyric acid (GABA) transport system. Cloning of two novel high affinity GABA transporters from rat brain. , 1992, The Journal of biological chemistry.

[176]  S. Grillner,et al.  Measured motion: searching for simplicity in spinal locomotor networks , 2009, Current Opinion in Neurobiology.

[177]  D. Lima,et al.  Local axon collaterals of lamina I projection neurons in the spinal cord of young rats , 2010, The Journal of comparative neurology.

[178]  T. Yamashita,et al.  BMP inhibition enhances axonal growth and functional recovery after spinal cord injury , 2008, Journal of neurochemistry.

[179]  Martin E Schwab,et al.  The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats , 2004, Nature Neuroscience.

[180]  K. Meiri,et al.  Nerve growth factor stimulation of GAP-43 phosphorylation in intact isolated growth cones , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[181]  D. Bredt,et al.  Characterization of MALS/Velis-1, -2, and -3: a Family of Mammalian LIN-7 Homologs Enriched at Brain Synapses in Association with the Postsynaptic Density-95/NMDA Receptor Postsynaptic Complex , 1999, The Journal of Neuroscience.

[182]  M. Filbin,et al.  A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration , 1994, Neuron.

[183]  Topographical organisation within the lateral reticular nucleus mossy fibre projection to the c1 and c2 zones in the rostral paramedian lobule of the cat cerebellum , 1997, The Journal of comparative neurology.

[184]  J. Fawcett Intrinsic neuronal determinants of regeneration , 1992, Trends in Neurosciences.

[185]  Integration in descending motor pathways controlling the forelimb in the cat. 4. Corticospinal inhibition of forelimb motoneurones mediated by short propriospinal neurones , 1978, Experimental Brain Research.

[186]  E Paul Zehr,et al.  Coordinated interlimb compensatory responses to electrical stimulation of cutaneous nerves in the hand and foot during walking. , 2003, Journal of neurophysiology.

[187]  W. Tetzlaff,et al.  Response of rubrospinal and corticospinal neurons to injury and neurotrophins. , 1994, Progress in brain research.

[188]  R. Deumens,et al.  Regeneration of descending axon tracts after spinal cord injury , 2005, Progress in Neurobiology.

[189]  Integration in descending motor pathways controlling the forelimb in the cat , 2004, Experimental Brain Research.

[190]  M. Eddleston,et al.  Molecular profile of reactive astrocytes—Implications for their role in neurologic disease , 1993, Neuroscience.

[191]  A Curt,et al.  From spinal shock to spasticity , 2000, Neurology.