Oligodendrocyte cytotoxic factor associated with fish optic nerve regeneration: implications for mammalian CNS regeneration

Cohen, A.; Sivron, Tomer; Duvdevani, Revital; Schwartz, Michal

doi:10.1016/0006-8993(90)90335-9

Cited by 39 publications

(15 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Monoclonal antibodies directed against the inhibitory molecules were shown to neutralize the growthinhibitory effect (10). In line with these observations is our finding that the high regenerative capacity of the fish optic nerve is correlated with the presence of a factor or factors cytotoxic to oligodendrocytes (12)(13)(14). This factor(s) was detected among the soluble substances derived from regenerating fish optic nerves, which were collectively termed conditioned medium (CM) and, when applied in vivo, helped to create conditions conducive to axonal growth in other species-e.g., in injured optic nerves of rabbit (15,16).…”

supporting

confidence: 78%

“…Independently, we showed that in vitro this preparation possesses a number of activities, including cytotoxicity to mature oligodendrocytes of both fish and rat (12)(13)(14). The observed correlation between the level of the cytotoxic factor and axonal regeneration in the fish strongly suggested an association between them (14).…”

Section: Discussionmentioning

confidence: 78%

“…RESULTS Presence of an IL-2-Like Molecule Cytotoxic to Oligodendrocytes in Fish CM. In a previous study we suggested that the cytotoxic factor(s) present in medium conditioned by regenerating fish optic nerves may belong to the lymphokine family (13,14). We investigated this possibility in the present study by examining whether treatment with antibodies against various cytokines would result in a loss of cytotoxic activity.…”

Section: Materials and Methods Preparation Of Soluble Substancesmentioning

confidence: 94%

“…Of the various antibodies tested-i.e., those directed against interleukins 6, 1, and 2 (IL-6, IL-1, and IL-2), platelet-derived growth factor (PDGF), and tumor necrosis factor, only the antibodies directed against IL-2 neutralized the cytotoxic effect of the CM. As for the presence of any of these factors in the fish CM, the binding assay revealed the presence of PDGF (22), which was shown independently to be devoid of any cytotoxic activity on oligodendrocytes (14). Negative results obtained for the other tested lymphokines do not necessarily imply their absence in the fish CM, as the results might derive from poor immunological crossreactivity due to species differences.…”

Section: Materials and Methods Preparation Of Soluble Substancesmentioning

confidence: 94%

“…This factor(s) was detected among the soluble substances derived from regenerating fish optic nerves, which were collectively termed conditioned medium (CM) and, when applied in vivo, helped to create conditions conducive to axonal growth in other species-e.g., in injured optic nerves of rabbit (15,16). Recent studies in our laboratory suggest that the cytotoxic factor(s) in the fish might be associated with the postinjury inflammatory reaction-i.e., with the early invasion of injured nerves by blood-derived cells (14). In the present study, the cytotoxic factor was identified as an interleukin 2 (IL-2)-like molecule.…”

mentioning

confidence: 92%

See 4 more Smart Citations

Identification of an interleukin 2-like substance as a factor cytotoxic to oligodendrocytes and associated with central nervous system regeneration.

Eitan

Zisling

Cohen

et al. 1992

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

View full text Add to dashboard Cite

Axons of the central nervous system in adult mammals do not regenerate spontaneously after injury, partly because of the presence of oligodendrocytes that inhibit axonal growth. This is not the case in lower vertebrates (e.g., in fish), where regeneration of the optic nerve does occur spontaneously and has been correlated with the presence of factors cytotoxic to oligodendrocytes. The present study provides evidence that the substance originating from the fish optic nerves, which is cytotoxic to oligodendrocytes, is an interleukin 2-like substance.Axons of the central nervous system (CNS) in lower vertebrates regenerate after injury (1-4). Considerable research interest has recently been focused on the oligodendrocytes. It was shown that mature oligodendrocytes create an environment that is nonpermissive for growth (9). Monoclonal antibodies directed against the inhibitory molecules were shown to neutralize the growthinhibitory effect (10). In line with these observations is our finding that the high regenerative capacity of the fish optic nerve is correlated with the presence of a factor or factors cytotoxic to oligodendrocytes (12)(13)(14). This factor(s) was detected among the soluble substances derived from regenerating fish optic nerves, which were collectively termed conditioned medium (CM) and, when applied in vivo, helped to create conditions conducive to axonal growth in other species-e.g., in injured optic nerves of rabbit (15, 16). Recent studies in our laboratory suggest that the cytotoxic factor(s) in the fish might be associated with the postinjury inflammatory reaction-i.e., with the early invasion of injured nerves by blood-derived cells (14). In the present study, the cytotoxic factor was identified as an interleukin 2 (IL-2)-like molecule. MATERIALS AND METHODSPreparation of Soluble Substances Derived from Regenerating Fish Optic Nerves. Carp (Cyprinus carpio, 800-1200 g; Tnuva, Israel) were anesthetized with 0.05% 3-aminobenzoic acid ethyl ester (Sigma), and their optic nerves were crushed with forceps (for 30 sec). Eight days later, the nerves were removed by dissection and incubated in serum-free medium for 1.5 hr (four nerve segments per 300 pLI of medium) at 250C (15). The resulting medium, defined as CM, was then collected, and its protein content was determined by the Bradford assay (17).Preparation of Medium Conditioned by Fish Lymphocytes. Fish were anesthetized with 3-aminobenzoic acid ethyl ester (Sigma). Blood was withdrawn from the venous plexus of the eye orbit and was collected (usually 30 ml from two or three fish) from the socket into a tube containing heparin sulfate (100 units/ml; BDH Chemicals). The blood was diluted with an equal volume of phosphate-buffered saline (PBS) and allowed to stand for 5 min before being layered on top of the Percoll solution [30 ml of diluted blood was carefully layered on top of the solution in a 50-ml sterilized Corex (Corning) centrifuge tube by using a small pipet]. The tubes were capped and centrifuged in swinging buckets at 800 x g ...

show abstract

supporting

confidence: 78%

Section: Discussionmentioning

confidence: 78%

Section: Materials and Methods Preparation Of Soluble Substancesmentioning

confidence: 94%

Section: Materials and Methods Preparation Of Soluble Substancesmentioning

confidence: 94%

mentioning

confidence: 92%

See 3 more Smart Citations

Identification of an interleukin 2-like substance as a factor cytotoxic to oligodendrocytes and associated with central nervous system regeneration.

Eitan

Zisling

Cohen

et al. 1992

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

View full text Add to dashboard Cite

show abstract

Growth of injured rabbit optic axons within their degenerating optic nerve

Lavie

Murray

Solomon

et al. 1990

J of Comparative Neurology

View full text Add to dashboard Cite

Spontaneous growth of axons after injury is extremely limited in the mammalian central nervous system (CNS). It is now clear, however, that injured CNS axons can be induced to elongate when provided with a suitable environment. Thus injured CNS axons can elongate, but they do not do so unless their environment is altered. We now show apparent regenerative growth of injured optic axons. This growth is achieved in the adult rabbit optic nerve by the use of a combined treatment consisting of: (1) supplying soluble substances originating from growing axons to be injured rabbit optic nerves (Schwartz et al., Science, 228:600-603, 1985), and (2) application of low energy He-Ne laser irradiation, which appears to delay degenerative changes in the injured axons (Schwartz et al., Lasers Surg. Med., 7:51-55, 1985; Assia et al., Brain Res., 476:205-212, 1988). Two to 8 weeks after this treatment, unmyelinated and thinly myelinated axons are found at the lesion site and distal to it. Morphological and immunocytochemical evidence indicate that these thinly myelinated and unmyelinated axons are growing in close association with glial cells. Only these axons are identified as being growing axons. These newly growing axons transverse the site of injury and extend into the distal stump of the nerve, which contains degenerating axons. Axons of this type could be detected distal to the lesion only in nerves subjected to the combined treatment. No unmyelinated or thinly myelinated axons in association with glial cells were seen at 6 or 8 weeks postoperatively in nerves that were not treated, or in nerves in which the two stumps were completely disconnected. Two millimeters distal to the site of injury, the growing axons are confined to a compartment comprising 5%-30% of the cross section of the nerve. A temporal analysis indicates that axons have grown as far as 6 mm distal to the site of injury, by 8 weeks postoperatively. Anterograde labeling with horseradish peroxidase, injected intraocularly, indicates that some of these newly growing axons arise from retinal ganglion cells.

show abstract

Cloning and characteristics of fish glial fibrillary acidic protein: Implications for optic nerve regeneration

Cohen

Shani

Schwartz

1993

J of Comparative Neurology

View full text Add to dashboard Cite

Mammalian central nervous system neurons do not regenerate after axonal injury, unlike their counterparts in fish and amphibians. After axonal injury, glial cells in mammals do not support regrowth of axons, while in fish they support the regeneration process. Controversy exists as to whether or not the intact fish optic nerve expresses glial fibrillary acidic protein, a well-known marker for mature astrocytes, and thus whether its astrocytes differ in this respect from those of the brain and spinal cord, as well as from optic nerve astrocytes of other species. In an attempt to resolve this question we cloned fish glial fibrillary acidic protein. Two different complementary DNA clones were isolated from a carp brain complementary DNA library, each encoding a different form of glial fibrillary acidic protein apparently originating from different genes. Monospecific polyclonal antibodies were raised against a peptide synthesized according to the predicted amino acid sequence, and used to identify and localize the fish glial fibrillary acidic protein. Two glial fibrillary acidic proteins (of 49 kDa and 51 kDa) were identified by the antibodies in all tested fish central nervous system tissues. The antibodies were then used to examine glial fibrillary acidic protein immunoreactivity in sections taken from uninjured and injured optic nerves of goldfish. Injury was followed by an elevation in glial fibrillary acidic protein immunoreactivity along the whole length of the nerve, except at the site of the injury, where--as in the case of vimentin--no immunoreactivity was detectable. However, in contrast to vimentin-positive glial cells, which repopulate the site of the injury soon after the optic nerve is injured, glial fibrillary acidic protein-positive glial cells remained outside the injury site for as long as 6 weeks after the injury. Despite the injury-induced changes in glial fibrillary acidic protein immunoreactivity, no change was observed in the level of transcript encoding glial fibrillary acidic protein after injury, while there was an increase in the amount of glial fibrillary acidic protein associated with the cytoskeleton and a reduction in the soluble form. These results suggest that the injury-induced changes in immunoreactivity on sections involve changes not in transcription or translation of glial fibrillary acidic protein, but in glial fibrillary acidic protein compartmentalization.

show abstract

Oligodendrocyte cytotoxic factor associated with fish optic nerve regeneration: implications for mammalian CNS regeneration

Cited by 39 publications

References 31 publications

Identification of an interleukin 2-like substance as a factor cytotoxic to oligodendrocytes and associated with central nervous system regeneration.

Identification of an interleukin 2-like substance as a factor cytotoxic to oligodendrocytes and associated with central nervous system regeneration.

Growth of injured rabbit optic axons within their degenerating optic nerve

Cloning and characteristics of fish glial fibrillary acidic protein: Implications for optic nerve regeneration

Contact Info

Product

Resources

About