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Effect of CNTF on ischaemic cell damage in rat hippocampus

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Summary

The neuroprotective effect of neurotrophic factors has been demonstrated in experimental cerebral ischaemia recently. These include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and basic fibroblast growth factor (basic FGF). The neuroprotective effect of ciliary neurotrophic factor (CNTF), however, has not been studied so far.

We have examined the neuroprotective effect of recombinant rat CNTF in a rat forebrain ischaemia model. A continuous infusion of CNTF was started 1 week before the induction of ischaemia and continued until 1 week after the ischaemia. Reversible forebrain ischaemia was induced by 7 minutes of bilateral carotid occlusion with hypotension. Neuronal cell death in the hippocampal CA1 sector was evaluated 1 week after the ischaemia. For the control group artificial CSF (cerebrospinal fluid) was infused instead of CNTF.

Per cent neuronal cell death was 83.4 ± 5.9% (mean ± SEM, n=5) in the control group, and 71.1 ± 10.0% (mean ± SEM, n=5) in the CNTF group. Although percentage of neuronal cell death was lower in the CNTF group, the difference was not statistically significant.

This result suggests that the protective effect of CNTF in the rat forebrain ischaemia model may be limited compared with other neurotrophic factors. It is considered that the number of neurons protected by CNTF may be small.

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References

  1. Beck T, Lindholm D, Castren E, Wree A (1994) Brain-derived neurotrophic factor protects against ischemic cell damage in rat hippocampus. J Cereb Blood Flow Metab 14: 689–692

    PubMed  Google Scholar 

  2. Clatterbuck RE, Price DL, Koliatsos VE (1993) Ciliary neurotrophic factor prevents retrograde neuronal death in the adult central nervous system. Proc Natl Acad Sci USA 90: 2222–2226

    PubMed  Google Scholar 

  3. Davis S, Aldrich TH, Valenzuela DM, Wong V, Furth ME, Squito SP, Yancopoulos GD (1991) The receptor for ciliary neurotrophic factor. Science 253: 59–63

    PubMed  Google Scholar 

  4. Gionet TX, Warner DS, Verhaegen M, Verhaegen M, Thomas JD, Todd MM (1992) Effect of intraischemic blood pressure on outcome from 2-vessel occlusion forebrain ischemia in the rat. Brain Res 586: 188–194

    PubMed  Google Scholar 

  5. Gluckman P, Klempt N, Guan J, Mallard C, Sirimanne E, Dragunow M, Klempt M, Singh K, Williams C, Nikolics K (1992) A role for IGF-1 in the rescue of CNS neurons following hypoxic-ischemic injury. Biochem Biophys Res Commun 182: 593–599

    PubMed  Google Scholar 

  6. Hagg T, Quon D, Higaki J, Varon S (1992) Ciliary neurotrophic factor prevents neuronal degeneration and promotes low affinity NGF receptor expression in the adult rat CNS. Neuron 8: 145–158

    PubMed  Google Scholar 

  7. Lindvall O, Ernfors P, Bengzon J, Kokaia Z, Smith ML, Siesjö BK (1992) Differential regulation of mRNAs for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the adult rat brain following cerebral ischemia and hypoglycaemic coma. Proc Natl Acad Sci USA 89: 648–652

    PubMed  Google Scholar 

  8. Masu Y, Wolf E, Holtmann B, Sendtner M, Brem G, Thoenen H (1993) Disruption of the CNTF gene results in motor neuron degeneration. Nature 365: 27–32

    PubMed  Google Scholar 

  9. Nakata N, Kato H, Kogure K (1993) Protective effects of basic fibroblast growth factor against hippocampal neuronal damage following cerebral ischemia in the gerbil. Brain Res 605: 354–356

    PubMed  Google Scholar 

  10. Nozaki K, Finklestein SP, Beal MF (1993) Basic fibroblast growth factor protects against hypoxia-ischemia and NMDA neurotoxicity in neonatal rats. J Cereb Blood Flow Metab 13: 221–228

    PubMed  Google Scholar 

  11. Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinate. Academic Press, New York

    Google Scholar 

  12. Sendtner M, Kreutzberg GW, Thoenen H (1990) Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy. Nature 345: 440–441

    PubMed  Google Scholar 

  13. Shigeno T, Mima T, Takakura K, Graham DI, Kato G, Hashimoto Y, Furukawa S (1991) Amelioration of delayed neuronal death in the hippocampus by nerve growth factor. J Neurosci 11: 2914–2919

    PubMed  Google Scholar 

  14. Skaper SD, Negro A, Dal Toso R, Facci L (1992) Recombinant human ciliary neurotrophic factor alters the threshold of hippocampal pyramidal neuron sensitivity to excitotoxin damage: synergistic effects of monosialogangliosides. J Neurosci Res 33: 330–337

    PubMed  Google Scholar 

  15. Smith ML, Bendek G, Dahlgren N, Rosén I, Wieloch T, Siesjö BK (1984) Models for studying long-term recovery following forebrain ischemia in the rat. 2: a 2-vessel occlusion model. Acta Neurol Scand 69: 385–401

    PubMed  Google Scholar 

  16. Stöckli KA, Lillien LE, Näher-Noe, Breitfeld G, Hughes RA, Raff MC, Thoenen H, Sendtner M (1991) Regional distribution, developmental changes, and cellular localization of CNTF-mRNA and protein in the rat brain. J Cell Biol 115: 447–459

    PubMed  Google Scholar 

  17. Stöckli KA, Lottspeich F, Sendtner M, Masiakowski P, Carroll P, Götz R, Lindholm D, Thoenen H (1989) Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor. Nature 343: 920–923

    Google Scholar 

  18. Takeda A, Onodera H, Sugimoto A, Kogure K, Obinata M, Shibahara S (1993) Coordinated expression of messenger RNAs for nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in the rat hippocampus following transient forebrain ischemia. Neuroscience 55: 23–31

    PubMed  Google Scholar 

  19. Tanaka K, Tsukahara T, Hashimoto N, Ogata N, Kimura T, Taniguchi T (1994) Effect of nerve growth factor on delayed neuronal death after cerebral ischemia. Acta Neurochir (Wien) 129: 64–71

    Google Scholar 

  20. Tsukahara T, Yonekawa Y, Tanaka K, Ohara O, Watanabe S, Kimura T, Nishijima T, Taniguchi T (1994) The role of brainderived neurotrophic factor in transient forebrain ischemia in the rat brain. Neurosurgery 34: 323–331

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosurgery, University Hospital of Zurich, Zurich, Switzerland

    N. Ogata, K. Ogata, H. G. Imhof & Y. Yonekawa

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  1. N. Ogata
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  2. K. Ogata
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  3. H. G. Imhof
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  4. Y. Yonekawa
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Ogata, N., Ogata, K., Imhof, H.G. et al. Effect of CNTF on ischaemic cell damage in rat hippocampus. Acta neurochir 138, 580–583 (1996). https://doi.org/10.1007/BF01411179

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