Summary
Grafts of optic nerve were placed end-toend with the proximal stumps of severed common peroneal nerves in inbred mice. It was found that fraying the proximal end of adult optic nerve grafts to disrupt the glia limitans increased their chances of being penetrated by regenerating peripheral nerve fibres. Suturing grafts to the proximal stump also enhanced their penetration by axons. The maximum distance to which the axons grew through the CNS tissue remained about 1.5 mm from 2–12 weeks after grafting. Schwann cells were seldom identified in the grafts. Varicose and degenerating nerve fibres were often seen within the grafts. Some varicose profiles were shown to be the terminal parts of axons within the grafts. Axons containing clusters of organelles resembling synaptic vesicles became more abundant in the longerterm grafts. Immunohistochemical studies performed on sutured grafts using a polyclonal antiserum to neurofilaments confirmed the impressions given by the electron microscopical observations. Grafts of neonatal optic nerve lacked myelin debris but were not usually penetrated by regenerating peripheral axons within a 6-week period. Sixty minutes after the intravenous injection of horseradish peroxidase, reaction product could be detected in the extracellular spaces around blood vessels in all types of living optic nerve graft. This indicates that blood-borne macromolecules could penetrate the grafts. However the profiles of axons which were found within living optic nerve grafts had no obvious relationship to blood vessels and were usually surrounded by astrocytic processes. These results suggest that living astrocytes, rather than the absence of serum-derived trophic factors or the presence of CNS myelin, constitute the major barrier to the extension of axons and the migration of Schwann cells into CNS tissue.
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References
Aguayo AJ (1985) Axonal regeneration from injured neurons in the adult mammalian central nervous system. In: Cotman CW (ed) Synaptic plasticity and remodelling. Guilford Press, London, pp 457–484
Aguayo AJ, Dickson R, Trecarten J, Attiwell M, Bray GM, Richardson P (1978) Ensheathment and myelination of regenerating PNS fibres by transplanted optic nerve glia. Neurosci Lett 9:97–104
Aguayo AJ, David S, Richardson P, Bray GM (1982) Axonal elongation in peripheral and central nervous system transplants. In: Fedoroff S, Hertz L (eds) Advances in cellular neurobiology, vol 3. Academic Press, New York, pp 215–234
Allcutt D, Berry M, Sievers J (1984) A quantitative comparison of the reactions of retinal ganglion cells to optic nerve crush in neonatal and adult mice. Dev Brain Res 16:219–230
Anderson PN, Turmaine M (1986) Peripheral nerve regeneration through grafts of living and freeze-dried CNS tissue. Neuropathol Appl Neurobiol 12:389–399
Anderson PN, Turmaine M (1987) Peripheral nerve fibres regenerate through myenteric plexus. Neurosci Lett 76:129–132
Anderson PN, Mitchell J, Mayor D, Stauber VV (1983) An ultrastructural study of the early stages of axonal regeneration through rat nerve grafts. Neuropathol Appl Neurobiol 9:455–466
Berry M (1983) Regeneration of axons in the central nervous system. In: Navaratnam V, Harrison RJ (eds) Progress in anatomy, vol 3. Cambridge University Press, London, pp 213–233
Blakemore WF (1976) Invasion of Schwann cells into the spinal cord of the rat following local injections of lysolethicin. Neuropathol Appl Neurobiol 2:21–39
Blakemore WF (1980) The effect of sub-dural nerve tissue transplantation in the spinal cord of the rat. Neuropathol Appl Neurobiol 6:433–447
Giftochristos N, David S (1988) Immature optic nerve glia of rat do not promote axonal regeneration when transplanted into a peripheral nerve. Dev Brain Res 39:149–153
Hall SM, Kent AP (1987) The response of regenerating peripheral neurites to a grafted optic nerve. J Neurocytol 16:317–331
Harvey AR, Gan SK, Dyson SE (1986) Regrowth of retinal axons after lesions of the brachium and pretectal region in the rat. Brain Res 368:141–147
Hopkins WG, Slack JR (1981) The sequential development of nodal sprouts in mouse muscles in response to nerve degeneration. J Neurocytol 10:537–556
Janzer RC, Raff MC (1987) Astrocytes induce blood-brain barrier properties in endothelial cells. Nature 325:253–257
Kiernan JA (1979) Hypotheses concerned with axonal regeneration in the mammalian nervous system. Biol Rev 54:155–197
Kiernan JA (1985) Axonal and vascular changes following injury to the rat's optic nerve. J Anat 141:139–154
Liuzzi FJ, Lasek RJ (1987) Astrocytes block axonal regeneration in mammals by activating the physiological stop pathway. Science 237:642–645
Mitchell J, Weller RO, Evans H (1979) Re-establishment of the blood-brain barrier to peroxidase following cold injury to mouse cortex. Acta Neuropathol (Berl) 46:45–49
Moore IE, Buontempo JM, Weller RO (1987) Response of fetal and neonatal rat brain to injury. Neuropathol Appl Neurobiol 13:219–228
Noble LJ, Maxwell DS (1983) Blood-spinal cord barrier response to transection. Exp Neurol 79:188–199
Olsson Y, Kristensson K (1973) Permeability of blood vessels and connective tissue sheaths in retina and optic nerve. Acta Neuropathol (Berl) 26:147–156
Reier PJ, Stensaas LJ, Guth L (1983) The astrocytic scar as an impediment to regeneration in the central nervous system. In: Kao CC, Bunge RP, Reier PJ (eds) Spinal cord reconstruction. Raven Press, New York, pp 163–195
Schwab ME, Theonen H (1985) Dissociated neurons regenerate into sciatic but not optic nerve explants in culture irrespective of neurotrophic factors. J Neurosci 5:2415–2423
So K-F, Schneider GE, Ayres S (1981) Lesions in the brachium of the superior colliculus in neonate hamsters: correlation of anatomy with behaviour. Exp Neurol 72:379–400
Stensaas LJ, Partlow LM, Burgess PR, Horch KW (1987) Inhibition of regeneration: the ultrastructure of reactive astrocytes and abortive axon terminals in the transition zone of the dorsal root. Prog Brain Res 71:457–468
Tolbert DL, Der T (1987) Redirected growth of pyramidal tract axons following neonatal pyramidectomy in cats. J Comp Neurol 260:299–311
Weinberg EL, Spencer PS (1979) Studies on the control of myelinogenesis. 3. Signalling of oligodendrocyte myelination by regenerating peripheral axons. Brain Res 162:273–279
Wujek JR, Reier PJ (1984) Astrocytic membrane morphology: differences between mammalian and amphibian astrocytes after axotomy. J Comp Neurol 222:607–619
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Anderson, P.N., Woodham, P. & Turmaine, M. Peripheral nerve regeneration through optic nerve grafts. Acta Neuropathol 77, 525–534 (1989). https://doi.org/10.1007/BF00687255
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DOI: https://doi.org/10.1007/BF00687255