Views on Regeneration in the Nervous System Kenneth J. Muller' and Albert J. Aguayo2
' Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida 33136; and 2Centre for Research in Neuroscience, McGill University and Montreal General Hospital, Montreal, Quebec, Canada H3G 1A4 The long, thin axons of nerve cells make them particularly vulnerable to injury. Furthermore, when in adult mammals the nervous system is damaged by trauma or disease, functional deficits tend to be permanent largely because lost neurons are not replaced and the regrowth of cut axons is often limited and inaccurate. While differences in size between the embryonic and adult nervous systems might partially explain the failure of damaged axons to replicate developmental patterns and grow back to their more distant targets, maturity seems to impose additional restrictions on natural repair. For example, central glia that ensheathe axons late in development appear to have the power to inhibit further growth by expressing specific molecules on their surface. A major challenge in neuroscience is to understand how neurons interact with these and other molecules in substrates and targets, both in intact and damaged nervous systems. It is anticipated that such insight will result in effective measures to enhance functional recovery after injury. Encouraging progress has been made on several fronts, and many of the accomplishments have been reviewed in recent reports from meetings and in reviews published in specialized volumes ( Abbott, 1991; Aguayo and Nicholls, 1991; Dunnett and Richards, 1990; Letourneau, Kater, and Macagno, 1991; Nicholls and Treherne, 1987; Orschot and Jones, 1990; Price and Bjorklund, 199 1 ; Stelzner, 1992; Timires, Privat, Giacobini, Lauder, and Vernadakis, I99 l ) . Our goal as editors of this special issue on neuronal regeneration has been to search for fresh perspectives and to combine the communication of new results and general views on selected topics relevant to this research field. In this issue of the Journul of Neurobiology, the initiation of axonal outgrowth and its extension are discussed in articles by Bixby, Brown, Masuda-Nakagawa, Stuermer, and their colleagues. Some of these, and articles by McKerracher, Richardson, and colleagues, examine differences in molecular mechanisms in different cell populations. The studies of Fishman and colleagues, who use a new technique of electroporation to introduce second messenger ana-
Journal of Neurobiology, Vol. 23, No. 5 , p. 467 (1992) 0 1992 John Wiley & Sons, Inc. CCC 0022-3034/92/050467-0l$O4.00
logues into cells, shed light on molecular controls of axon extension and on plastic changes in neural connections. Several of the articles, including those by Bixby, Carbonetto, and their collaborators, reshape popular conceptions concerning molecular controls of growth. Exciting data on the roles of non-neuronal cells are presented by Brown, Masuda-Nakagawa, Stuermer, and their coworkers. New understanding of target recognition, including specific signals that stop growth, and molecular mechanisms for synapse stabilization are among the important contributions of Mason, Wallace, and their colleagues. It is clear from these and other contributions that the field of neural regeneration is active. Advances will continue to come from painstaking research on many fronts.
REFERENCES ABBOTT,N. J., Ed. ( 1991). Glial-neuronal interactions in regeneration. In: Glial-Neuronal Interactions (special issue). Ann. N Y Acad. Sci. 633:209-244. AGUAYO,A. J. and NICHOLLS, J. G., Eds. ( 1991 ). Development and regeneration of the nervous system. Phil. Trans. Roy. Soc. Lond. B 331:253-350. DUNNETT,S. B. and RICHARDS, S.-J., Eds. (1990). Neural Transplantation: From Molecular Basis to Clinical Applications (special issue). Prog. Bruin Rex 82~1-743. LETOURNEAU, P., KATER,S., and MACAGNO, E. R., Eds. ( 199 1 ). Nerve regeneration. In The Growth Cone, Raven Press, New York, pp. 449-517. NICHOLLS,J. and TREHERNE, J., Eds. (1987). Neural Repair (special issue). J. Exp. Biol. 132:l-289. ORSCHOT,D. E. and JONES, D. G. ( 1990). Axonal regeneration in the mammalian central nervous system. Adv. Anat. Embryol. Cell Biol. 119:l-118. PRICE,D. L. and BJORKLUND, A., Eds. ( 199 1 ). Disease, Transplantation and Regeneration (special issue). Curr. Opin. Neurobiol. 1:399-467, 501-552. STELZNER, D. J., Ed. ( 1992). Repair ofcentral Nervous System (special issue). Exp. Neurol. 115:109- 192. TIMIRAS, P. S., PRIVAT, A., GIACOBINI, E., LAUDER, J., and VERNADAKIS, A., Eds. ( 1991). Plasticity and Regeneration ofthe Nervous System (special issue). Adv. Exptl. Med. Bid. 296: 1-365. 467
' Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida 33136; and 2Centre for Research in Neuroscience, McGill University and Montreal General Hospital, Montreal, Quebec, Canada H3G 1A4 The long, thin axons of nerve cells make them particularly vulnerable to injury. Furthermore, when in adult mammals the nervous system is damaged by trauma or disease, functional deficits tend to be permanent largely because lost neurons are not replaced and the regrowth of cut axons is often limited and inaccurate. While differences in size between the embryonic and adult nervous systems might partially explain the failure of damaged axons to replicate developmental patterns and grow back to their more distant targets, maturity seems to impose additional restrictions on natural repair. For example, central glia that ensheathe axons late in development appear to have the power to inhibit further growth by expressing specific molecules on their surface. A major challenge in neuroscience is to understand how neurons interact with these and other molecules in substrates and targets, both in intact and damaged nervous systems. It is anticipated that such insight will result in effective measures to enhance functional recovery after injury. Encouraging progress has been made on several fronts, and many of the accomplishments have been reviewed in recent reports from meetings and in reviews published in specialized volumes ( Abbott, 1991; Aguayo and Nicholls, 1991; Dunnett and Richards, 1990; Letourneau, Kater, and Macagno, 1991; Nicholls and Treherne, 1987; Orschot and Jones, 1990; Price and Bjorklund, 199 1 ; Stelzner, 1992; Timires, Privat, Giacobini, Lauder, and Vernadakis, I99 l ) . Our goal as editors of this special issue on neuronal regeneration has been to search for fresh perspectives and to combine the communication of new results and general views on selected topics relevant to this research field. In this issue of the Journul of Neurobiology, the initiation of axonal outgrowth and its extension are discussed in articles by Bixby, Brown, Masuda-Nakagawa, Stuermer, and their colleagues. Some of these, and articles by McKerracher, Richardson, and colleagues, examine differences in molecular mechanisms in different cell populations. The studies of Fishman and colleagues, who use a new technique of electroporation to introduce second messenger ana-
Journal of Neurobiology, Vol. 23, No. 5 , p. 467 (1992) 0 1992 John Wiley & Sons, Inc. CCC 0022-3034/92/050467-0l$O4.00
logues into cells, shed light on molecular controls of axon extension and on plastic changes in neural connections. Several of the articles, including those by Bixby, Carbonetto, and their collaborators, reshape popular conceptions concerning molecular controls of growth. Exciting data on the roles of non-neuronal cells are presented by Brown, Masuda-Nakagawa, Stuermer, and their coworkers. New understanding of target recognition, including specific signals that stop growth, and molecular mechanisms for synapse stabilization are among the important contributions of Mason, Wallace, and their colleagues. It is clear from these and other contributions that the field of neural regeneration is active. Advances will continue to come from painstaking research on many fronts.
REFERENCES ABBOTT,N. J., Ed. ( 1991). Glial-neuronal interactions in regeneration. In: Glial-Neuronal Interactions (special issue). Ann. N Y Acad. Sci. 633:209-244. AGUAYO,A. J. and NICHOLLS, J. G., Eds. ( 1991 ). Development and regeneration of the nervous system. Phil. Trans. Roy. Soc. Lond. B 331:253-350. DUNNETT,S. B. and RICHARDS, S.-J., Eds. (1990). Neural Transplantation: From Molecular Basis to Clinical Applications (special issue). Prog. Bruin Rex 82~1-743. LETOURNEAU, P., KATER,S., and MACAGNO, E. R., Eds. ( 199 1 ). Nerve regeneration. In The Growth Cone, Raven Press, New York, pp. 449-517. NICHOLLS,J. and TREHERNE, J., Eds. (1987). Neural Repair (special issue). J. Exp. Biol. 132:l-289. ORSCHOT,D. E. and JONES, D. G. ( 1990). Axonal regeneration in the mammalian central nervous system. Adv. Anat. Embryol. Cell Biol. 119:l-118. PRICE,D. L. and BJORKLUND, A., Eds. ( 199 1 ). Disease, Transplantation and Regeneration (special issue). Curr. Opin. Neurobiol. 1:399-467, 501-552. STELZNER, D. J., Ed. ( 1992). Repair ofcentral Nervous System (special issue). Exp. Neurol. 115:109- 192. TIMIRAS, P. S., PRIVAT, A., GIACOBINI, E., LAUDER, J., and VERNADAKIS, A., Eds. ( 1991). Plasticity and Regeneration ofthe Nervous System (special issue). Adv. Exptl. Med. Bid. 296: 1-365. 467
