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Comparative protective effects of vinconate, baclofen, and pentobarbital against neuronal damage following repeated brief cerebral ischemia in the gerbil brain

Research in Experimental Medicine volume 191, Article number: 371 (1991) Cite this article

Summary

We investigated the neuroprotective effects of vinconate (a vinca alkaloid derivative), baclofen (a GABAB receptor agonist), or pentobarbital (a GABAA receptor-effector) on neuronal damage following repeated brief cerebral ischemia in the gerbils. The animals were allowed to survive for 7 days after two or three 2-min ischemic insults induced by bilateral occlusion of the common carotid arteries. Morphological changes were evaluated in hippocampal CA1 sector and selectively vulnerable areas after two or three 2-min ischemic insults at 1-h intervals, respectively. Pretreatment with vinconate significantly reduced histopathological neuronal damage to the hippocampal CA1 sector following two 2-min ischemic insults. However, pretreatment with baclofen and pentobarbital failed to prevent neuronal damage. Pretreatment with vinconate also prevented neuronal damage to the frontal cortex, parietal cortex, and striatum following three 2-min ischemic insults. Nevertheless, this drug failed to prevent neuronal damage to the hippocampal CA1 sector and the thalamus. Results suggest that vinconate, a vica alkaloid derivative, can prevent neuronal damage after repeated brief cerebral ischemia, but not GABAergic agents, such as baclofen and pentobarbital. These findings are of interest in relation to the mechanisms of neuronal damage induced by repeated brief cerebral ischemia.

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References

  1. Araki T, Kogure K (1989) Prevention of delayed neuronal death in gerbil hippocampus by a novel vinca alkaloid derivative (vonconate). Mol Chem Neuropathol 11: 33–43

    PubMed  CAS  Article  Google Scholar 

  2. Araki T, Kato H, Kogure K (1989) Selective neuronal vulnerability following transient cerebral ischemia in the gerbil: distribution and time course. Acta Neurol Scand 80: 548–553

    PubMed  CAS  Google Scholar 

  3. Araki T, Kato H, Inoue T, Kogure K (1990) Regional impairment of protein synthesis following brief cerebral ischemia in the gerbil. Acta Neuropathol 79: 501–505

    PubMed  Article  CAS  Google Scholar 

  4. Araki T, Kato H, Kogure K (1990) Neuronal damage and calcium accumulation following repeated brief cerebral ischemia in the gerbil. Brain Res 528: 114–122

    PubMed  Article  CAS  Google Scholar 

  5. Araki T, Kato H, Kogure K, Inoue T (1990) Regional neuroprotective effects of pentobarbital on ischemia-induced brain damage. Brain Res Bull 25: 861–865

    PubMed  Article  CAS  Google Scholar 

  6. Araki T, Kogure K, Murakami M (1991) Prevention of abnormal calcium accumulation in postischemic gerbil brain by vinconate. Acta Neurol Scand 83: 155–160

    PubMed  CAS  Article  Google Scholar 

  7. Araki T, Kato H, Hara H, Kogure K (1991) Postischemic alteration of [3H]forskolin binding sites in selectively vulnerable areas: an autoradiographic study of gerbil brain. Neurosci Lett 125: 159–162

    PubMed  Article  CAS  Google Scholar 

  8. Buchan A, Pulsinelli WA (1990) Hypothermia but not the N-Methyl-d-aspartate antagonist, MK-801, attenuates neuronal damage in gerbils subjected to transient global ischemia. J Neurosci 10: 311–316

    PubMed  CAS  Google Scholar 

  9. Corbett D, Evans S, Thomas C, Wang D, Jonas RA (1990) MK-801 reduced cerebral ischemic injury by inducing hypothermia. Brain Res 514: 300–304

    PubMed  Article  CAS  Google Scholar 

  10. Crain BJ, Westerkam WD, Harrison AH, Nadler JV (1988) Selective neuronal death after transient forebrain ischemia in the Mongolian gerbil: a silver impregnation study. Neuroscience 27: 387–402

    PubMed  Article  CAS  Google Scholar 

  11. Ikeda J, Nagashima G, Nowak TS, Mies G, Joo F, Xu S, Lohr J, Ruetzler C, Wagner HG, Klatzo I (1989) Observations on accumulation of calcium in gerbils subjected to cerebral ischemia. In: Krieglstein J (ed) Pharmacology of cerebral ischemia 1988. Proceedings of the Second International Symposium on Pharmacology of Cerebral Ischemia, CRC Press, Florida, pp 37–44

    Google Scholar 

  12. Kato H, Kogure K (1990) Neuronal damage following non-lethal but repeated cerebral ischemia in the gerbil. Acta Neuropathol 79: 494–500

    PubMed  Article  CAS  Google Scholar 

  13. Kato H, Kogure K, Nakano S (1989) Neuronal damage following repeated brief ischemia in the gerbil. Brain Res 479: 366–370

    PubMed  Article  CAS  Google Scholar 

  14. Kato H, Araki T, Kogure K, Murakami M, Uemura K (1990) Sequential cerebral blood flow changes during and after nonlethal cerebral ischemia in gerbils. Stroke 21: 1346–1349

    PubMed  CAS  Google Scholar 

  15. Kárpáti E, Szporny L (1976) General and cerebral haemodynamic activity of ethy apovincaminate. Arzneimittelforschung 26: 1908–1912

    PubMed  Google Scholar 

  16. Katsuragi T, Ohba M, Mori R, Kushiku K, Furukawa T (1984) Calcium antagonistic action involved in vasodilation by brovincamine. Gen Pharmacol 15:43–45

    PubMed  CAS  Google Scholar 

  17. Kirino T, Tamura A, Sano K (1986) A reversible type of neuronal injury following ischemia in the gerbil hippocampus. Stroke 17: 455–459

    PubMed  CAS  Google Scholar 

  18. Kitagawa K, Matsumoto M, Ninobe M, Mikoshiba K, Hata R, Ueda H, Handa N, Fukunaga R, Isaka Y, Kimura K, Kamada T (1989) Microtuble-associated protein 2 as a sensitive marker for cerebral ischemic damage-immunohistochemical investigation of dendritic damage. Neuroscience 31: 401–411

    PubMed  Article  CAS  Google Scholar 

  19. Olpe HR, Steinmann MW (1982) The effects of vincamine, hydrgine and piracetam on firing rate of locus coeruleus neurons. J Neural Transm 55: 101–109

    PubMed  Article  CAS  Google Scholar 

  20. Pulsinelli WA, Brierley JB, Plum F (1982) Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol 11: 491–498

    PubMed  Article  CAS  Google Scholar 

  21. Sauer D, Rischke R, Beck T, Roßberg C, Mennel HD, Bielenberg GW, Krieglstein J (1988) Vinpocetine prevents ischemic cell damage in rat hippocampus. Life Sci 43: 1733–1739

    PubMed  Article  CAS  Google Scholar 

  22. Sternau LL, Lust WD, Ricci AJ, Racheson R (1989) Role for γ-aminobutyric acid in selective vulnerability in gerbils. Stroke 20: 281–287

    PubMed  CAS  Google Scholar 

  23. Tomida S, Nowak TS, Vass K, Lohr JM, Klatzo I (1987) Experimental model for repetitive ischemic attacks in the gerbil: the cumulative effect of repeated ischemic insults. J Cereb Blood Flow Metab 7: 773–782

    PubMed  CAS  Google Scholar 

  24. Welsh FA, Sims RE, Harris VA (1990) Mild hypothermia prevents ischemic injury in gerbil hippocampus. J Cereb Blood Flow Metab 10: 557–563

    PubMed  CAS  Google Scholar 

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Affiliations

  1. Department of Neurology, Institute of Brain Diseases, Tohoku University, School of Medicine, Sendai, Japan

    T. Araki, H. Kato & K. Kogure

Authors
  1. T. Araki
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  2. H. Kato
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  3. K. Kogure
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Araki, T., Kato, H. & Kogure, K. Comparative protective effects of vinconate, baclofen, and pentobarbital against neuronal damage following repeated brief cerebral ischemia in the gerbil brain. Res. Exp. Med. 191, 371 (1991). https://doi.org/10.1007/BF02576692

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  • DOI: https://doi.org/10.1007/BF02576692

Key words

  • Cerebral ischemia
  • Repeated ischemia
  • Selective vulnerability
  • Vinca alkaloid
  • GABAergic agent
  • Gerbil