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. 1993 Feb;13(1):15–23. doi: 10.1007/BF00712986

Increased production of endothelins in the hippocampus of stroke-prone spontaneously hypertensive rats following transient forebrain ischemia: Histochemical evidence

Kimihiro Yamashita 1,, Yasufumi Kataoka 1, Masami Niwa 1, Kazuto Shigematsu 2, Akihiko Himeno 3, Shuichi Koizumi 4, Kohtaro Taniyama 1
PMCID: PMC11566809  PMID: 8458060

Abstract

  1. The effect of transient forebrain ischemia on endothelin-1 (ET-1) and endothelin-3 (ET-3) production in the hippocampus of stroke-prone spontaneously hypertensive rats (SHRSPs) was investigated using immunohistochemical techniques.

  2. In SHRSPs subjected to 10-min bilateral carotid occlusion, neuronal degeneration in the CA1 pyramidal cell layer of the hippocampus was detectable at 4 days and remarkable at 7 days after reperfusion.

  3. Coinciding with neuronal degeneration, ET-1- and ET-3-like immunoreactivities were intense in the CA1 pyramidal-cell layer, the stratum lacunosum moleculare, and the CA4 subfield of the hippocampus. Almost all of the immunostained cells had morphological characteristics of astrocytes.

  4. The possibility that ET has a role in the development of neuronal cell death following transient forebrain ischemia warrants further attention.

Key words: endothelin-1, endothelin-3, transient forebrain ischemia, delayed neuronal death, hippocampus, stroke-prone spontaneously hypertensive rat, immunohistochemistry

References

  1. Arai, H., Hori, S., Aramori, I., Ohkubo, H., and Nakanishi, S. (1990). Cloning and expression of a cDNA encoding an endothelin receptor.Nature348730–732. [DOI] [PubMed] [Google Scholar]
  2. Chan, J., and Greenberg, D. A. (1991). Endothelin and calcium signalling in NG108-15 neuroblastoma × glioma cells.J. Pharmacol. Exp. Ther.258524–530. [PubMed] [Google Scholar]
  3. Choi, D. W., Maulucci-Gedde, M., and Kriegstein, A. R. (1987). Glutamate neurotoxicity in cortical cell culture.J. Neurosci.7357–368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cintra, A., Fuxe, K., Änggård, E., Tinner, B., Staines, W., and Agnati, L. F. (1989). Increased endothelin-like immunoreactivity in ibotenic acid-lesioned hippocampal formation of the rat brain.Acta Physiol. Scand.137557–558. [DOI] [PubMed] [Google Scholar]
  5. Deshpande, J. K., Siesjö, B. K., and Wieloch, T. (1987). Calcium accumulation and neuronal damage in the rat hippocampus following cerebral ischemia.J. Cereb. Blood Flow Metab.789–95. [DOI] [PubMed] [Google Scholar]
  6. Ehrenreich, H., Kehrl, J. H., Anderson, R. W., Rieckmann, P., Vitkovic, L., Coligan, J. E., and Fauci, A. S. (1991). A vasoactive peptide, endothelin-3, is produced by and specifically binds to primary astrocytes.Brain Res.53854–58. [DOI] [PubMed] [Google Scholar]
  7. Fuxe, K., Cintra, A., Andbjer, B., Änggård, E., Goldstein, M., and Agnati, L. F. (1989). Centrally administered endothelin-1 produces lesions in the brain of the male rat.Acta Physiol. Scand.137155–156. [DOI] [PubMed] [Google Scholar]
  8. Giaid, A., Gibson, S. J., Herrero, M. T., Gentleman, S., Legon, S., Yanagisawa, M., Masaki, T., Ibrahim, N. B. N., Roberts, G. W., Rossi, M. L., and Polak, J. M. (1991). Topographical localisation of endothelin mRNA and peptide immunoreactivity in neurones of the human brain.Histochemistry95303–314. [DOI] [PubMed] [Google Scholar]
  9. Goldstein, G. W., and Betz, A. L. (1986). The blood-brain barrier.Sci. Am.25570–79. [DOI] [PubMed] [Google Scholar]
  10. Horie, R. (1977). Cerebral circulation and the initiation mechanism of stroke in stroke-prone spontaneously hypertensive rats (SHRSP).Jap. Circ. J.41915–935. [DOI] [PubMed] [Google Scholar]
  11. Ibaragi, M., Niwa, M., and Ozaki, M. (1989). Atrial natriuretic peptide-induced inhibition of amiloride-sensitive22Na+ uptake into cerebral capillaries of spontaneously hypertensive rats.Jap. J. Pharmacol.5082–85. [DOI] [PubMed] [Google Scholar]
  12. Inoue, A., Yanagisawa, M., Kimura, S., Kasuya, Y., Miyauchi, T., Goto, K., and Masaki, T. (1989). The human endothelin family: Three structurally and pharmacologically distinct isopeptides predicted by three separate genes.Proc. Natl. Acad. Sci. USA862863–2867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kataoka, Y., Koizumi, S., Kumakura, K., Kurihara, M., Niwa, M., and Ueki, S. (1989). Endothelin-triggered brain damage under hypoglycemia evidenced by real-time monitoring of dopamine release from rat striatal slices.Neurosci. Lett.10775–80. [DOI] [PubMed] [Google Scholar]
  14. Lustig, H. S., Chan, J., and Greenberg, D. A. (1992). Comparative neurotoxic potential of glutamate, endothelins, and platelet-activating factor in cerebral cortical cultures.Neurosci. Lett.13915–18. [DOI] [PubMed] [Google Scholar]
  15. MacCumber, M. W., Ross, C. A., and Snyder, S. H. (1990). Endothelin in brain: Receptors, mitogenesis, and biosynthesis in glial cells.Proc. Natl. Acad. Sci. USA872359–2363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Marsault, R., Vigne, P., Breittmayer, J.-P., and Frelin, C. (1990). Astrocytes are target cells for endothelins and sarafotoxin.J. Neurochem.542142–2144. [DOI] [PubMed] [Google Scholar]
  17. Nishimura, T., Akasu, T., and Krier, J. (1991). Endothelin modulates calcium channel current in neurones of rabbit pelvic parasympathetic ganglia.Br. J. Pharmacol.1031241–1250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Niwa, M., Kawaguchi, T., Yamashita, K., Maeda, T., Kurihara, M., Kataoka, Y., and Ozaki, M. (1991). Specific125I-endothelin-1 binding sites in the central nervous system.Clin. Exp. Hypertens.A13799–806. [DOI] [PubMed] [Google Scholar]
  19. Niwa, M., Kawaguchi, T., Himeno, A., Fujimoto, M., Kurihara, M., Yamashita, K., Kataoka, Y., Shigematsu, K., and Taniyama, K. (1992). Specific binding sites for125I-endothelin-1 in the porcine and human spinal cord.Eur. J. Pharmacol. Mol. Pharmacol.225281–289. [DOI] [PubMed] [Google Scholar]
  20. Okamoto, K., Yamori, Y., and Nagaoka, A. (1974). Establishment of the stroke-prone spontaneously hypertensive rat (SHR).Circ. Res.34 (Suppl. 1):143–153.4272692 [Google Scholar]
  21. Onodera, H., Sato, G., and Kogure, K. (1986). Lesions to Schaffer collaterals prevent ischemic death of CA1 pyramidal cells.Neurosci. Lett.68169–174. [DOI] [PubMed] [Google Scholar]
  22. Pulsinelli, W. A., and Brierley, J. B. (1979). A new model of bilateral hemispheric ischemia in the unanesthetized rat.Stroke10267–272. [DOI] [PubMed] [Google Scholar]
  23. Qiang, W.-G., Ikeda, K., Nara, Y., Horie, R., and Yamori, Y. (1989). Delayed neuronal death by transient ligations of bilateral carotid arteries in SHRSR, SHRSP and WKY.Jap. Heart J.30582. [Google Scholar]
  24. Reiser, G., and Donié, F. (1990). Endothelin induces a rise of inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate levels and of cytosolic Ca2+ activity in neural cell lines,Eur. J. Neurosci.2769–775. [DOI] [PubMed] [Google Scholar]
  25. Sakurai, T., Yanagisawa, M., Takuwa, Y., Miyazaki, H., Kimura, S., Goto, K., and Masaki, T. (1990). Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor.Nature348732–735. [DOI] [PubMed] [Google Scholar]
  26. Smith, M.-L., Auer, R. N., and Siesjö, B. K. (1984). The density and distribution of ischemic brain injury in the rat following 2–10 min of forebrain ischemia.Acta Neuropathol.64319–332. [DOI] [PubMed] [Google Scholar]
  27. Uchida, S., Ohta, H., Niwa, M., Mori, A., Nonaka, G., Nishioka, I., and Ozaki, M. (1990). Prolongation of life span of stroke-prone spontaneously hypertensive rats (SHRSP) ingesting persimmon tannin.Chem. Pharm. Bull.381049–1052. [DOI] [PubMed] [Google Scholar]
  28. Vigne, P., Marsault, R., Breittmayer, J. P., and Frelin, C. (1990). Endothelin stimulates phosphatidylinositol hydrolysis and DNA synthesis in brain capillary endothelial cells.Biochem. J.266415–420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Vigne, P., Ladoux, A., and Frelin, C. (1991). Endothelins activate Na+/H+ exchange in brain capillary endothelial cells via a high affinity endothelin-3 receptor that is not coupled to phospholipase C.J. Biol. Chem.2665925–5928. [PubMed] [Google Scholar]
  30. Yanagisawa, M., Kurihara, H., Kimura, S., Tomobe, Y., Kobayashi, M., Mitsui, Y., Yazaki, Y., Goto, K., and Masaki, T. (1988). A novel potent vasoconstrictor peptide produced by vascular endothelial cells.Nature332411–415. [DOI] [PubMed] [Google Scholar]
  31. Yoshizawa, T., Kimura, S., Kanazawa, I., Uchiyama, Y., Yanagisawa, M., and Masaki, T. (1989). Endothelin localizes in the dorsal horn and acts on the spinal neurones: Possible involvement of dihydropyridine-sensitive calcium channels and substance P release.Neurosci. Lett.102179–184. [DOI] [PubMed] [Google Scholar]
  32. Yoshizawa, T., Shinmi, O., Giaid, A., Yanagisawa, M., Gibson, S. J., Kimura, S., Uchiyama, Y., Polak, J. M., Masaki, T., and Kanazawa, I. (1990). Endothelin: A novel peptide in the posterior pituitary system.Science247462–464. [DOI] [PubMed] [Google Scholar]

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