Acta Neuropathologica

, Volume 49, Issue 3, pp 177–185 | Cite as

Vascular permeability and axonal regeneration in tissues autotransplanted into the brain

  • E. A. Heinicke
Original Works


Pieces of skin, peripheral nerve, muscle, tendon, thyroid gland, and submandibular gland were autotransplanted into the brains of mice. The animals were killed after 5-week periods. Fluorescently labelled albumin was injected i.v. 1 h prior to death. Silver-impregnated sections were examined under the light microscope for the regeneration of axons from the brains into the implanted tissues. Unstained sections were studied by fluorescence microscopy for the presence of the labelled tracer in the extracellular spaces of the grafts. The muscle and submandibular gland received the fewest regenerating axons, skin and tendon received an intermediate amount of reinnervation, and the thyroid gland and vagus nerve were the most richly innervated. The amount of reinnervation could be roughly correlated with the presence of extravascular protein within the tissues. These data support the hypothesis that regeneration of axons may be dependent upon a source of protein in the extracellular fluid surrounding their growing tips.

Key words

Axonal regeneration Central axons Intracerebral tissue Grafts Vascular permeability 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bakay L (1972) Alteration of the brain barrier system in pathological states. In: Lajtha A (ed) Handbook of neurochemistry. Plenum Press. New York London, pp 417–427Google Scholar
  2. Barnard, JW, Carpenter W (1950) Lack of regeneration in the spinal cord of rat. J Neurophysiol 13:223–228Google Scholar
  3. Björklund A, Stenevi U (1971) Growth of central catecholamine neurons into smooth muscle grafts in the rat mesencephalon. Brain Res 31:1–20Google Scholar
  4. Björklund A, Bjerre B, Stenevi U (1973) Has nerve growth factor a role in the regeneration of central and peripheral catecholamine neurons? In: Fuxe K, Olson L, Zotterman Y (eds) Dynamics of degeneration and growth in neurons. Pergamon Press, Oxford New York Toronto Sydney, pp 389–409Google Scholar
  5. Cason JE (1951) A rapid one-step Mallory-Heidenhein stain for connective tissue. Stain Technol 25:225–226Google Scholar
  6. Cockett SA, Kiernan JA (1973) Acceleration of peripheral nervous regeneration in the rat by exogenous triiodothyronine. Exp Neurol 39:389–394Google Scholar
  7. Endo M (1964) Entry of a dye into the sarcotubular system of muscle. Nature 202:1115–1116Google Scholar
  8. Erikson LB, Glees P (1953) Sprouting of cortical nerve fibers following skin homografts into the cerebral cortex. J Physiol 120:17P (Abstract)Google Scholar
  9. Fertig A, Kiernan JA, Seyan SSAS (1971) Enhancement of axonal regeneration in the brain of the rat by corticotrophin and triiodothyronine. exp Neurol 33:372–385Google Scholar
  10. Glees P (1955) Studies of cortical regeneration with special reference to cerebral implants. In: Windle WF (ed) Regeneration in the central nervous system. Thomas, Springfield, Illinois, pp 94–111Google Scholar
  11. Glees P, Erikson L (1953) Untersuchungen über die Regenerationsfähigkeit der Hirnrinde nach experimenteller Einpflanzung von Haut in das Hirngewebe des Kaninchens. Verh Anat Ges 51:101–111. Quoted in Glees P (1955)Google Scholar
  12. Griffiths IR, Miller R (1974) Vascular permeability to protein and vasogenic oedema in experimental concussive injuries to the canine spinal cord. J Neurol Sci 22:291–304Google Scholar
  13. Ham AW (1974) Histology, 7th edn. Lippincot, Philadelphia Toronto, p 369Google Scholar
  14. Harvey JE, Srebnik HH (1967) Locomotor activity and axon regeneration following spinal cord compression in rats treated withl-thyroxine. J Neuropathol Exp Neurol 26:661–668Google Scholar
  15. Heinicke E (1977) Influence of exogenous triiodothyronine on axonal regeneration and wound healing in the brain of the rat. J Neurol Sci 31:293–305Google Scholar
  16. Heinicke EA, Kiernan JA (1978) Vascular permeability and axonal regeneration in skin autotransplanted into the brain. J Anat 125:409–420Google Scholar
  17. Hill DK (1964) The space accessible to albumin within the striated muscle fibre of the toad. J Physiol 175:275–294Google Scholar
  18. Hogg RM, Simpson R (1975) An evaluation of solochrome cyanine RS as a nuclear stain similar to haematoxylin. Med Lab Technol 32:301–306Google Scholar
  19. Holmes W (1943) Silver staining of nerve axons in paraffin sections. Anat Rec 86:157–187Google Scholar
  20. Horvat J-C (1965) Incitation expérimentale de la régénération cérébelleuse chez la souris par greffe bréphoplastique de glande sous-maxillaire. CR Assoc Anat 49:836–848Google Scholar
  21. Horvat J-C (1966) Comparaison des réactions régénératives provoquées dans le cerveau et dans le cervelet de la souris par des greffes tissulaires intraraciales. CR Assoc Anat 51:487–499Google Scholar
  22. Horvat J-C (1967a) Reactions régénératives provoquées au niveau de la moelle épinière thoracique de la souris par la greffe de nerfs et de quelques tissus non nerveux. CR Assoc Anat 52:659–669Google Scholar
  23. Horvat J-C (1967b) Réactions régénératives provoquées dans le cervelet de la souris par des greffes tissulaires homoplastiques et bréphoplastiques. Arch Sci Physiol 21:323–343Google Scholar
  24. Horvat J-C (1969) Aspects ultrastructuraux de la réhabiation de fragments de glande sous-maxillaire transplantés dans la moelle épinière de la souris, par des fibres nerveuses d'origine centrale. CR Assoc Anat 54:218–230Google Scholar
  25. Huxley HE (1964) Evidence for continuity between the central elements of the triads and extracellular space in frog sartorius muscle. Nature 202:1067–1071Google Scholar
  26. Kao CC (1974) Comparison of healing process in transected spinal cords grafted with autogenous brain tissue, sciatic nerve, and nodose ganglion. Exp Neurol 44:424–439Google Scholar
  27. Kao CC, Chang LW, Bloodworth JMB (1977) Axonal regeneration across transected mammalian spinal cords: an electron microscopic study of delayed microsurgical nerve grafting. Exp Neurol 54:591–615Google Scholar
  28. Karnovsky MJ (1965) Vesicular transport of exogenous peroxidase across capillary endothelium into the T system of muscle. J Cell Biol 27:49A-50A (Abstract)Google Scholar
  29. Kiernan JA (1969) Studies on nervous regeneration. Ph. D. thesis, University of BirminghamGoogle Scholar
  30. Kiernan JA (1978) An explanation of axonal regeneration in peripheral nerves and its failure in the central nervous system. Med Hypotheses 4:15–26Google Scholar
  31. Kiernan JA (1979) Production and life span of cutaneous mast cells in young rats. J Anat 128:225–238Google Scholar
  32. Klatzo I, Miquel J (1960) Observations on pinocytosis in nervous tissue. J Neuropathol Exp Neurol 19:475–487Google Scholar
  33. Klatzo I, Miquel J, Otenaser R (1962) The application of fluoresceinlabeled serum proteins (FLSP) to the study of vascular permeability in the brain. Acta Neuropathol (Berl) 2:144–160Google Scholar
  34. Lee J, Olszewski J (1959) Permeability of cerebral blood vessels in healing of brain wounds. Neurology (Minneap) 9:7–14Google Scholar
  35. Le Gros Clark WE (1942) The problem of neuronal regeneration in the central nervous system. I. The influence of spinal ganglia and nerve fragments grafted in the brain. J Anat 77:20–48Google Scholar
  36. Le Gros Clark WE (1943) The problem of neuronal regeneration in the central nervous system. II. The insertion of peripheral nerve stumps into the brain. J Anat 77:251–259Google Scholar
  37. Libelius R, Josefsson J-O, Lundquist I (1979) Endocytosis in chronically denervated mouse skeletal muscle. A biochemical and ultrastructural study with horseradish peroxidase. Neurosci 4:283–292Google Scholar
  38. Melsaac G, Kiernan JA (1975a) Accelerated recovery from peripheral nerve injury in experimental hyperthyroidism. Exp Neurol 48:88–94Google Scholar
  39. McIsaac G, Kiernan JA (1975b) Acceleration of neuromuscular reinnervation by triiodothyronine. J Anat 120:551–560Google Scholar
  40. McQuarric IG (1975) Nerve regeneration and thyroid hormone treatment. J Neurol Sci 26:499–502Google Scholar
  41. Medawar PB (1948) Immunity to homologous grafted skin. III. The fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br J Exp Pathol 29:58–69Google Scholar
  42. Nairn RC (1976) Fluorescent protein tracing, 4th edn. Churchill Livingstone, Edinburgh London, New YorkGoogle Scholar
  43. Nathaniel EJH, Clemente CD (1959) Growth of nerve fibers into skin and muscle grafts in rat brains. Exp Neurol 1:65–81Google Scholar
  44. Olsson Y, Hossmann K-A (1970) Fine structural localization of exudated protein tracers in the brain. Acta Neuropathol (Berl) 16:103–116Google Scholar
  45. Page S (1964) The organization of the sarcoplasmic reticulum in frog muscle. J Physiol 175:10P-11PGoogle Scholar
  46. Persson L, Hansson H-A, Sourander P (1976) Extravasation, spread, and cellular uptake of Evans blue-labelled albumin around a reproducible small stab-wound in the rat brain. Acta Neuropathol (Berl) 34:125–136Google Scholar
  47. Rinder L, Olsson Y (1968) Studies on vascular permeability changes in experimental brain concussion. Acta Neuropathol (Berl) 11:183–200Google Scholar
  48. Shirai S (1935) Experimentelle Untersuchungen über die Degenerations- und Regenerationsvorgänge der Nervenfasern im intrazerebral transplantierten Gewebe. Mitt Med Akad Kioto 14:226–250. Quoted in Glees P (1955)Google Scholar
  49. Sugar O, Gerard RW (1940) Spinal cord regeneration in the rat. J Neurophysiol 3:1–19Google Scholar
  50. Tello F (1911) La influencia del neurotropismo en la regeneración de los centros nerviosos. Trab Lab Invest Biol (Univ. Madrid) 9:123. Quoted in Le Gros Clark WE (1942)Google Scholar
  51. Van Gilder JC, Schwartz HG (1967) Growth of dermoids from skin implants to the nervous system and surrounding spaces of the newborn rat. J Neurosurg 26:14–24Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • E. A. Heinicke
    • 1
  1. 1.Department of Anatomy, Health Sciences CentreThe University of Western OntarioLondonCanada

Personalised recommendations