Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 May;118(1):33–40. doi: 10.1111/j.1476-5381.1996.tb15363.x

Effects of delayed treatment with nafronyl oxalate on microsphere embolism-induced changes in monoamine levels of rat brain regions.

N Takagi 1, K Miyake 1, A Ohiwa 1, R Nukaga 1, S Takeo 1
PMCID: PMC1909473  PMID: 8733573

Abstract

1. The present study was undertaken to examine the effects of delayed treatment with nafronyl oxalate (nafronyl), a cerebral vasodilator, on monoamine neurotransmitters of brain regions in the microsphere-embolized rat. 2. Microsphere embolism was induced by injecting 900 microspheres with a diameter of 48 microns into the right internal carotid artery of rats. Microsphere-embolized rats were treated with nafronyl, 15 mg kg-1, i.p., twice daily from the first to the 5th day. Levels of monoamines and their metabolites in the cerebral cortex, striatum, and hippocampus were measured on days 3 and 5 after the operation by a high-performance liquid chromatograph with electrochemical detection. In vivo tyrosine or tryptophan hydroxylation was estimated by measurement of the accumulation of 3, 4-dihydroxyphenylalanine or 5-hydroxy-1-tryptophan after administration of 3-hydroxybenzylhydrazine dihydrochloride, an inhibitor of aromatic L-amino acid decarboxylase. 3. Microsphere embolism induced decreases in dopamine, noradrenaline and 5-hydroxytryptamine in three brain regions of the right hemisphere on days 3 and 5. In the left hemisphere, the monoamines were reduced, but to a lesser degree than in the right hemisphere. On days 3 and 5, the decrease in the monoamines of the right hemisphere was attenuated by nafronyl treatment except for noradrenaline on day 3. The decrease in the monoamines levels in the left hemisphere was almost completely prevented by nafronyl treatment. 4. On day 3 after microsphere embolism, in vivo tyrosine and tryptophan hydroxylation was lower than the pre-embolic value in all three brain regions. Treatment of the embolized rats with nafronyl significantly attenuated the decrease in in vivo tyrosine and tryptophan hydroxylation in the ipsilateral hemisphere, but not hippocampal tryptophan hydroxylation. 5. The results suggested that treatment with nafronyl improves or attenuates changes in monoamine neurotransmitter metabolism of the brain regions impaired by microsphere embolism. The mechanisms underlying this effect may be attributed to preservation of the ability to synthesize monoamines when the brain is ischaemic or oligaemic.

Full text

PDF
33

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Admani A. K. New approach to treatment of recent stroke. Br Med J. 1978 Dec 16;2(6153):1678–1679. doi: 10.1136/bmj.2.6153.1678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Furlow T. W., Jr, Bass N. H. Arachidonate-induced cerebrovascular occlusion in the rat. The role of platelets and aspirin in stroke. Neurology. 1976 Apr;26(4):297–304. doi: 10.1212/wnl.26.4.297. [DOI] [PubMed] [Google Scholar]
  3. Iijima S., Hara K., Suga H., Nakamura S., Kameyama M. Effect of ischemia on hydroxylase cofactor (tetrahydrobiopterin) and monoamine neurotransmitters in rat brain. Stroke. 1986 May-Jun;17(3):529–533. doi: 10.1161/01.str.17.3.529. [DOI] [PubMed] [Google Scholar]
  4. Kirino T. Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res. 1982 May 6;239(1):57–69. doi: 10.1016/0006-8993(82)90833-2. [DOI] [PubMed] [Google Scholar]
  5. Kogure K., Scheinberg P., Matsumoto A., Busto R., Reinmuth O. M. Catecholamines in experimental brain ischemia. Arch Neurol. 1975 Jan;32(1):21–24. doi: 10.1001/archneur.1975.00490430043005. [DOI] [PubMed] [Google Scholar]
  6. McGraw C. P. Experimental cerebral infarctioneffects of pentobarbital in Mongolian gerbils. Arch Neurol. 1977 Jun;34(6):334–336. doi: 10.1001/archneur.1977.00500180028006. [DOI] [PubMed] [Google Scholar]
  7. Miyake K., Taguchi T., Tanonaka K., Horiguchi T., Takagi N., Takeo S. Beneficial effects of naftidrofuryl oxalate on brain regional energy metabolism after microsphere-induced cerebral embolism. J Pharmacol Exp Ther. 1992 Mar;260(3):1058–1066. [PubMed] [Google Scholar]
  8. Miyake K., Takagi N., Takeo S. Effects of naftidrofuryl oxalate on microsphere embolism-induced decrease in regional blood flow of rat brain. Br J Pharmacol. 1994 May;112(1):226–230. doi: 10.1111/j.1476-5381.1994.tb13056.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Miyake K., Takeo S., Kaijihara H. Sustained decrease in brain regional blood flow after microsphere embolism in rats. Stroke. 1993 Mar;24(3):415–420. doi: 10.1161/01.str.24.3.415. [DOI] [PubMed] [Google Scholar]
  10. Miyake K., Tanonaka K., Minematsu R., Inoue K., Takeo S. Possible therapeutic effect of naftidrofuryl oxalate on brain energy metabolism after microsphere-induced cerebral embolism. Br J Pharmacol. 1989 Oct;98(2):389–396. doi: 10.1111/j.1476-5381.1989.tb12609.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mrsulja B. B., Mrsulja B. J., Spatz M., Klatzo I. Action of cerebral ischemia on decreased levels of 3-methoxy-4-hydroxy-phenylethylgylcol sulfate, homovanillic acid and 5-hydroxy-indoleacetic acid produced by pargyline. Brain Res. 1975 Nov 14;98(2):388–393. doi: 10.1016/0006-8993(75)90020-7. [DOI] [PubMed] [Google Scholar]
  12. Naritomi H. Experimental basis of multi-infarct dementia: memory impairments in rodent models of ischemia. Alzheimer Dis Assoc Disord. 1991 Summer;5(2):103–111. doi: 10.1097/00002093-199100520-00007. [DOI] [PubMed] [Google Scholar]
  13. Pulsinelli W. A., Brierley J. B., Plum F. Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol. 1982 May;11(5):491–498. doi: 10.1002/ana.410110509. [DOI] [PubMed] [Google Scholar]
  14. Siesjö B. K. Brain energy metabolism and catecholaminergic activity in hypoxia, hypercapnia and ischemia. J Neural Transm Suppl. 1978;(14):17–22. [PubMed] [Google Scholar]
  15. Smith M. L., Auer R. N., Siesjö B. K. The density and distribution of ischemic brain injury in the rat following 2-10 min of forebrain ischemia. Acta Neuropathol. 1984;64(4):319–332. doi: 10.1007/BF00690397. [DOI] [PubMed] [Google Scholar]
  16. Taguchi T., Miyake K., Tanonaka K., Okada M., Takagi N., Fujimori K., Takeo S. Sustained changes in acetylcholine and amino acid contents of brain regions following microsphere embolism in rats. Jpn J Pharmacol. 1993 Jul;62(3):269–278. doi: 10.1254/jjp.62.269. [DOI] [PubMed] [Google Scholar]
  17. Taguchi T., Takagi N., Miyake K., Tanonaka K., Okada M., Kajihara H., Takeo S. Effects of naftidrofuryl oxalate on microsphere-induced changes in acetylcholine and amino acid content of rat brain regions. Exp Brain Res. 1994;99(1):7–16. doi: 10.1007/BF00241407. [DOI] [PubMed] [Google Scholar]
  18. Takeo S., Taguchi T., Tanonaka K., Miyake K., Horiguchi T., Takagi N., Fujimori K. Sustained damage to energy metabolism of brain regions after microsphere embolism in rats. Stroke. 1992 Jan;23(1):62–68. doi: 10.1161/01.str.23.1.62. [DOI] [PubMed] [Google Scholar]
  19. Takeo S., Tanonaka R., Miyake K., Tanonaka K., Taguchi T., Kawakami K., Ono M., Hiramatsu M., Okano K. Naftidrofuryl oxalate improves impaired brain glucose metabolism after microsphere-induced cerebral embolism in rats. J Pharmacol Exp Ther. 1991 Apr;257(1):404–410. [PubMed] [Google Scholar]
  20. Uemura Y., Miller J. M., Matson W. R., Beal M. F. Neurochemical analysis of focal ischemia in rats. Stroke. 1991 Dec;22(12):1548–1553. doi: 10.1161/01.str.22.12.1548. [DOI] [PubMed] [Google Scholar]
  21. Welch K. M., Chabi E., Buckingham J., Bergin B., Achar V. S., Meyer J. S. Cathecholamine and 5-hydroxytryptamine levels in ischemic brain. Influence of p-chlorophenylalanine. Stroke. 1977 May-Jun;8(3):341–346. doi: 10.1161/01.str.8.3.341. [DOI] [PubMed] [Google Scholar]
  22. Young A. R., Barry D. I., MacKenzie E. T., Robert J. P. Cerebro-circulatory effects of so-called 'vasodilators' in the anaesthetised rat. Eur Neurol. 1983;22(2):142–153. doi: 10.1159/000115551. [DOI] [PubMed] [Google Scholar]
  23. Zervas N. T., Hori H., Negora M., Wurtman R. J., Larin F., Lavyne M. H. Reduction in brain dopamine following experimental cerebral ischaemia. Nature. 1974 Feb 1;247(5439):283–284. doi: 10.1038/247283a0. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES