Abstract
Study design:
Review.
Objectives:
To examine the state of research in central nervous system (CNS) regeneration and to suggest an alternative to the sterile research at the lesion site.
Setting:
Worldwide.
Methods:
A search of publications using ‘PubMed’ and a search of the historical literature relevant to CNS regeneration, biological models, the neurone theory, collateral sprouting, spinal shock and the central pattern generator.
Results:
There is no evidence for CNS regeneration.
Conclusion:
A century of research focussed on the lesion site has been unproductive. An alternative field of research must be developed and the best candidate is the undamaged CNS.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Fawcett J . Repair of spinal cord injuries: where are we, where are we going? Spinal Cord 2002; 40: 615–623.
Tsai EC, Krassioukov AV, Tator CH . Corticospinal regeneration into lumbar grey matter correlates with locomotor recovery after complete spinal cord transection and repair with peripheral nerve grates, fibroblast growth factor 1, fibrin glue and spinal fusion. J Neurpathol Ex Neuro 2005; 64: 230–244.
Kadoya K, Tsukada S, Lu P, Coppola G, Geschwind D, Filbin M et al. Combined intrinsic and extrinsic neuronal mechanisms facilitate bridging axonal regeneration one year after spinal cord injury. Neuron 2009; 64: 165–172.
Vidal-Sanz M, Bray GM, Villegas-Perez MP, Thanos S, Aguayo AJ . Axonal regeneration and synapse formation in the superior colliculus by retinal ganglion cells in the adult rat. J Neurosci 1987; 7: 2894–2909.
Lui K, Lu Y, Lee JK, Samara R, Willenberg R, Sears-Kraxberger I et al. PTEN depletion enhances the regenerative ability of adult corticospinal neurons. Nat Neurosci 2010; 13: 1075–1081.
Liu K, Tedeschi A, Park KK, He Z . Neuronal intrinsic mechanisms of axon regeneration. Ann Rev Neurosoc 2011; 34: 131–152.
Stahnisch FW, Nitsch R . Santiago Ramon y Cajal's concept of neurological plasticity. Trends Neurosci 2002; 25: 589–591.
Wang D, Sun T . Neural plasticity and functional recovery of human central nervous system with special reference to spinal cord injury. Spinal Cord 2011; 49: 486–492.
Merrill EG, Wall PD . Plasticity of connections in the adult nervous system. In: Cotman CW (ed). Neuronal Plasticity 1978. Raven Press: New York, 97–111.
Illis LS . Enlargement of spinal cord synapses after repetitive stimulation. Nature 1969; 223: 76–77.
von Monakow C . Der Grosshirn und die Abbaufunktion durch kortikale 1914. Bergman.Herde: Wiesbaden.
Freud S . Quoted by E Jones in ‘The Life and Work of Sigmund Freud’. 1953. Basic Books Inc.: New York.
Illis LS . The motor neuron surface and spinal shock. In: Williams D (ed). Modern Trends in Neurology, vol. 4. 1967. Butterworths: London, pp 53–68.
Young JZ . Growth and plasticity in the nervous system. Proc Roy Soc 1951; B139: 18–37.
Wyckoff RWG, Young JZ . The motoneuron surface. Proc Roy Soc 1956; B144: 440–450.
Eccles JC . The Physiology of Synapses 1964. Springer-Verlag: Berlin.
Armstrong J, Richardson KC, Young JZ . Staining neural end feet and mitochondria after post-chroming and carbowax embedding. Stain Technol 1956; 31: 263–270.
Fitzsimons JTR, Illis LS, Mitchell J . Silver deposition in synaptic vesicles using the Armstrong-Stephens stain. Brain Res 1974; 72: 277–281.
Aitken JT, Bridger JE . Neuron size and neuron population density in the lumbosacral region of the cat's spinal cord. J Anat 1961; 95: 38–53.
Illis LS . Spinal cord synapses in the cat. The normal appearances by the light microscope. Brain 1964; 87: 543–554.
Liu Cnchambers WW . Intraspinal sprouting of dorsal root axons Arch. Neurol Psychiat 1958; 79: 46–61.
Illis LS, Patangia GN, Cavanagh JB . Boutons termineaux and tri-ortho-cresyl phosphate toxicity. Exp Neurol 1966; 14: 160–174.
Raisman G . Neuronal plasticity in the septal nuclei of the adult rat. Brain Res 1969; 14: 25–48.
Illis LS . Spinal cord synapses in the cat: the reaction of boutons termineaux at the motoneuron surface to experimental denervation. Brain 1964; 87: 55–572.
Illis LS . Experimental model of regeneration in the CNS. I Synaptic Changes Brain 1973; 96: 47–60.
Illis LS . Experimental model of regeneration in the CNS. II. The reaction of glia. Brain 1973; 96: 61–68.
Sherrington CS . The Integrative Action of the Nervous System. Cambridge University Press: Cambridge, 1947 p 245.
Illis LS . Changes in spinal cord synapses and possible explanation for spinal shock. Exp Neurol 1963; 8: 328–335.
Ruch TC . Medical Physiology and Biophysics. Saunders: Philadelphia, 1960.
Creed RS, Denny-Brown D, Eccles JC, Liddell EGT, Sherrington CS . Reflex Activity of the Spinal Cord. Oxford University Press: Oxford, 1932.
Teasdell RD, Stavraky GW . Responses of the de-afferented spinal neurones to cortico-spinal impulses. J Neurophysiol 1953; 16: 367–375.
Gray EG, Hamlyn LH . Election microscopy of experimental degeneration in the avian optic tectum. J Anat 1962; 96: 309–316.
Raisman G . A promising therapeutic approach to spinal cord repair. J R Soc Med 2003; 96: 259–261.
Bach-Y-Rita P, Illis LS . Spinal shock: possible role of receptor plasticity and non-synpatic transmission. Paraplegia 1993; 31: 82–87.
Miller S Scott PD . The spinal locomotor generator. Exp Brain Res 1977; 30: 387–403.
Shik ML, Orlovski GN, Severin FV . Locomotion in the mesencephalic cat elicited by stimulation of the pyramids. Biophysics 1968; 13: 143–152.
Shefchyk SJ, Jordan LM . Excitatory and inhibititory postsynaptic potentials in alpha motoneurons produced during fictive locomotion by stimulation of the mesencephalic locomotor region. J Neurophsiol 1958; 53: 1345–1355.
Fossberg H, Grillner S . The locomotion of the acute spinal cat injected with clonidine I. V Brain Res 1973; 50: 184–186.
Barbeau H, Chan C, Rossignol S . Noradrenergic agonists and locomotor training effect locomotor recovery after cord transection in adult cats. Brain Res Bull 1993; 30: 387–393.
Wernig A, Muller S . Laufband locomotion with body weight support improved walking in persons with severe spinal cord injuries. Paraplegia 1992; 30: 229–238.
Dietz V, Colombo G, Jensen L . Locomotor activity in spinal man. Lancet 1994; 344: 1260–1263.
Dimitrijevic MR, Gerasimenko Y, Pinter MM . Evidence for a spinal central pattern generator in humans. Ann N Y Acad Sci 1998; 16: 360–376.
Illis LS . Recovery in the CNS and the experimental background of central functional simulation in spinal cord dysfunction. In: Illis LS (ed). Chapter 1 in Spinal Cord Dysfunction. Oxford University Press: Oxford, 1992, 9–37.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The author declares no conflict of interest.
Rights and permissions
About this article
Cite this article
Illis, L. Central nervous system regeneration does not occur. Spinal Cord 50, 259–263 (2012). https://doi.org/10.1038/sc.2011.132
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sc.2011.132
Keywords
This article is cited by
-
Long-term clinical observation of patients with acute and chronic complete spinal cord injury after transplantation of NeuroRegen scaffold
Science China Life Sciences (2022)
-
Restoration versus reconstruction: cellular mechanisms of skin, nerve and muscle regeneration compared
Regenerative Medicine Research (2013)
-
Radial glial cells play a key role in echinoderm neural regeneration
BMC Biology (2013)
