Morphological response of injured adult rabbit optic nerve to implants containing media conditioned by growing optic nerves

Lavie, Vered; Harel, A.; Doron, Amihood; Solomon, Arieh S.; Lobel, David; Belkin, Michael; Benbasat, S.; Sharma, S. C.; Schwartz, Michal

doi:10.1016/0006-8993(87)90580-4

Cited by 25 publications

(7 citation statements)

References 16 publications

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“…Thus, regeneration seems to represent for the central nerve system (CNS) a favorable situation for producing (or enhancing production of) growth factors. In the same manner, it was established that factors that allow the regeneration of mammalian CNS axons (which are known for their limited ability to recover after injury) are produced by regenerating or growing nerves, such as crushed optic nerves of mature goldfish or optic nerves of the newborn rabbit [13,15,18,22].…”

Section: Modulation Of Mitogenic Activity Of Spinal Cord During LImentioning

confidence: 99%

Blastema cell proliferation in vitro: Effects of limb amputation on the mitogenic activity of spinal cord extracts

Boilly

Albert

1988

Biology of the Cell

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Primary cultures of mesenchymal cells of axolotl limb blastemas provide a very sensitive in vitro bioassay for studying nerve dependence of newt regeneration. These cells can be stimulated by crude spinal cord extracts of non-amputated animals in a dose-dependent manner up to 60 micrograms protein/ml of culture medium; at this concentration the mitotic index is increased 4-fold. Spinal cord extracts of axolotls 14 days after forelimb amputation (i.e., late bud stage) are more efficient in stimulating blastema cell proliferation (+50%) than extracts of axolotls 7 days after forelimb amputation (i.e., early bud stage) or of axolotls without amputation. In a similar manner, spinal cord extracts of young axolotls 14 days after forelimb amputation, are more stimulatory than older axolotls 14 d after forelimb amputation which regenerate only a very small blastema during the same time. It appears that spinal cord mitogenic activity is enhanced after limb amputation, probably in correlation with blastema cell requirements for limb regeneration.

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Section: Modulation Of Mitogenic Activity Of Spinal Cord During LImentioning

confidence: 99%

Blastema cell proliferation in vitro: Effects of limb amputation on the mitogenic activity of spinal cord extracts

Boilly

Albert

1988

Biology of the Cell

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“…Such factors might be involved in activation of the potentially scarforming cells and in affecting the motility they need for migration. In line with this notion are studies demonstrating that soluble substances derived from regenerating fish optic nerve promote growth of injured rabbit optic axons across the site of injury and as much as 6mm into the distal segment of the injured nerve (Lavie et al, 1987(Lavie et al, , 1990. The same soluble substances also modulate the behavior of glial cells in vitro.…”

Section: Glial Response To Injury In the Rat And Fishmentioning

confidence: 76%

Glial cell types, lineages, and response to injury in rat and fish: Implications for regeneration

Sivron

Schwartz

1995

Glia

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Axons of the mammalian central nervous system do not regenerate spontaneously after axonal injury, unlike the central nervous system axons of fish and amphibians and the peripheral nervous system of mammals, which possess a good regenerative ability (Grafstein: The Retina: A Model for Cell Biology Studies, Part II, 1986; Kiernan: Biol Rev 54:155-197, 1979; Murray: J Comp Neurol 168:175-196, 1976; Ramón y Cajal: Degeneration and Regeneration of the Nervous System, 1928; Reier and Webster: J Neurocytol 3:591-618, 1974; Sperry: Physiol Zool 23:351-361, 1948). It was previously believed that intrinsic differences between the central nervous system neurons of mammals and fish account for their differences in regenerative ability. The past decade, however, has seen an accumulation of evidence, indicating that mammalian central nervous system neurons are able to regenerate injured axons, at least to some extent. This was first demonstrated by Aguayo and colleagues (David and Aguayo: Science 214:931-933, 1981; Kierstead et al: Science 246:255-257, 1989), who showed that injured mammalian central nervous system axons can grow for a considerable distance into an autograft of a peripheral nerve. It was also demonstrated that injured rabbit optic axons can regenerate into their own environment (i.e., into the distal part of the injured optic nerve), if the injured nerve is treated so as to make it conducive for growth (Lavie et al: J Comp Neurol 298:293-314, 1990; Eitan et al: Science 264:1764-1768, 1994).(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Our previous morphological observations revealed, in GATF-treated nerves but not in untreated injured nerves, growth cones embedded in astrocytic processes (14). This by itself suggests that the proliferating cells do not necessarily impede growth and even can support regeneration by forming a scaffold for the growing fibers, provided that they acquire the appropriate properties.…”

Section: Discussionmentioning

confidence: 99%

“…Both regenerating nerves of fish and developing nerves of rabbit were found to be sources for these active regeneration-triggering factors, called growth-associated triggering factors (GATFs) (1,2). The response induced by GATFs included biochemical changes in the rabbit retina, sprouting activity in vitro and in situ, and promotion of survival of ganglion cells and nerve fibers (1,2,14). Upon exposure to the active implant, the injured nerves themselves became producers of their own GATFs (1), thus suggesting that the inability of the injured rabbit nerves to produce these factors can be functionally circumvented.…”

mentioning

confidence: 99%

Environmental changes induced by growth-associated triggering factors in injured optic nerve of adult rabbit.

Bawnik¹,

Harel²,

Stein-Izsak³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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Central nervous system (CNS) neurons of mammals regenerate poorly after axonal injury. However, if an injured CNS neuron (rabbit optic nerve) is supplied with appropriate soluble substances ("growth-associated triggering factors") derived from medium conditioned by regenerating fish optic nerve or newborn rabbit optic nerve, it can express regeneration-associated characteristics. Such characteristics include a general increase in protein synthesis, changes in synthesis of specific polypeptides, and sprouting of nerve fibers in culture. The present study of rabbit optic nerves demonstrates that such active substances affect the neuronal environment (i.e., the non-neuronal cells), thereby perhaps causing a shift in the environment from an inhibitory to a regenerative supportive one. Apparently, such an environment is spontaneously achieved in injured CNS nerves of lower vertebrates (e.g., fish optic nerves), which are regenerable. Treatment of injured rabbit optic nerve with soluble factors from medium conditioned by regenerating carp optic nerve resulted in a selective increase in proliferation ([3H]thymidine incorporation) of perineural cells and the appearance of a 12-kDa polypeptide in a homogenate derived from the nerve and its associated cells. This polypeptide may be related to growth, since it comigrates in NaDodSO4/polyacrylamide gel electrophoresis with a 12-kDa polypeptide that is continuously present in a regenerative system. In addition, there were injuryinduced changes in the polypeptides of the nerve that were independent of treatment with conditioned medium and were correlated with nerve maturation. The most prominent changes of this type were in 18-kDa and 25-kDa polypeptides whose levels were reduced after injury and were found to be correlated with the nerve maturation (myelination) state.The loss of function that results from damage to the central nervous system (CNS) of mammals is due to the low regenerative potential of the mammalian CNS. Recent observations have offered new clues as to why the adult CNS fails to regenerate (1-6). It appears that the environment of the injured neuron is involved in determining the ability of the neuron to regenerate after injury. The contribution of the environment (i.e., the non-neuronal cells) to the process of regeneration is possibly in provision of diffusible substances (7, 8) and a proper extracellular matrix needed to induce and support the regenerative cascade (6, 9).Studies carried out in regenerative peripheral (sciatic nerve of rat) and central (optic nerve of fish) nerves have provided evidence that injury causes changes in the type and amount of diffusible molecules originating from non-neuronal cells surrounding the injured nerves. In the peripheral nervous system, a 37-kDa polypeptide was found to be selectively accumulated following injury to the sciatic nerve (10) and was identified recently as a form of apolipoprotein E (11, 12).Studies in our laboratory have demonstrated that, in the regenerating optic nerves of fish, there are alte...

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Morphological response of injured adult rabbit optic nerve to implants containing media conditioned by growing optic nerves

Cited by 25 publications

References 16 publications

Blastema cell proliferation in vitro: Effects of limb amputation on the mitogenic activity of spinal cord extracts

Blastema cell proliferation in vitro: Effects of limb amputation on the mitogenic activity of spinal cord extracts

Glial cell types, lineages, and response to injury in rat and fish: Implications for regeneration

Environmental changes induced by growth-associated triggering factors in injured optic nerve of adult rabbit.

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