Skip to main content
SpringerLink
Log in

Alterations of local cerebral blood flow, phorbol 12,13-dibutyrate binding activity, and histological damage during acute focal ischaemia in rat brain

A pathophysiology of acute focal ischaemia: Part 1

  • Published:
Acta Neurochirurgica Aims and scope Submit manuscript

Summary

The alterations of the local cerebral blood flow (LCBF),3 H-phorbol 12,13-dibutyrate (PDBu) binding activity were measured, and histological findings were also examined during the closed time course (0, 1, 3, 5, 7 hour) after middle cerebral artery occlusion (MCAO) in rat brain to assess the complex pathophysiology of acute focal ischaemia. From 1 to 3 hours after the start of MCAO, significant (p < 0.01) hyperreactivity of the second messenger system involving PDBu binding may be present, despite low perfusion of LCBF, and severe damage in the striatum whereas sparing almost completely the cortex on histological examination. At 5 hours, the PDBu binding activity increased slightly but not significantly but is reduced markedly at 7 hours after MCAO compared with the control group. The measurement of PDBu binding activity, additionally to measuring the LCBF and observation of the histological change might be a useful indicator in determining the threshold and duration of ischaemia which cause functionally irreversible cell damage in the brain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Astrup J, Symon L, Branston NM (1977) Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. Stroke 8: 51–57

    PubMed  Google Scholar 

  2. Astrup J, Siesjo BK, Symon L (1981) Thresholds in cerebral ischemia — the ischemie penumbra. Stroke 12: 723–725

    PubMed  Google Scholar 

  3. Branston NM, Strong AJ, Symon L (1977) Extracellular potassium activity, evoked potential and tissue blood flow: relationship during progressive ischemia in baboon cerebral cortex. J Neurol Sci 32: 305–321

    PubMed  Google Scholar 

  4. Chiou WJ, Leach KL (1991) Action of protein kinase C by H202 in UCIIMG astrocytes. Soc Neurosci Abst 17: 1087

    Google Scholar 

  5. Farooqui AA, Horrocks LA (1991) Excitatory amino acid receptors, neural membrane phospholipid metabolism and neurological disorders. Brain Res Rev 16: 171–191

    PubMed  Google Scholar 

  6. Favaron M, Manev H, Siman R, Bertolino M, Szekely AM, DeErausquin G, Guidotti A, Costa E (1990) Down-regulation of protein kinase C cerebellar granule neurons in primary culture from glutamate-induced neuronal death. Proc Natl Acad Sci USA 87: 1983–1987

    PubMed  Google Scholar 

  7. Garcia JH, Lossinsky AS, Kaufmann FC, Conger KA (1978) Neuronal ischemie injury: light microscopy, ultrastructure and biochemistry. Acta Neuropathol 43: 85–95

    PubMed  Google Scholar 

  8. Hakim AM, Hogan MJ, Carpenter S (1992) Time course of cerebral blood flow and histological outcome after focal cerebral ischemia in rats. Stroke 23: 1138–1144

    PubMed  Google Scholar 

  9. Hara H, Onodera H, Yoshidomi M, Matsuda Y, Kogure K (1990) Staurosporine, a novel protein kinase C inhibitor, prevents postischemic neuronal damage in the gerbil rat. J Cereb Blood Flow Metab 10: 646–653

    PubMed  Google Scholar 

  10. Hara H, Onodera H, Kato H, Araki T, Kogure K (1991) Autoradiographic analysis of second messenger and neurotransmitter system receptors in the gerbil hippocampus following transient forebrain ischemia. Brain Res 545: 87–96

    PubMed  Google Scholar 

  11. Heiss WD, Hayakawa T, Waltz AG (1976) Patterns of changes of blood flow and relationship to infarction in experimental cerebral ischemia. Stroke 7: 454–459

    Google Scholar 

  12. Heiss WD, Rosener G (1983 a) Functional recovery of cortical neurons as related to degree and duration of ischemia. Ann Neurol 14: 299–301

    Google Scholar 

  13. Heiss WD (1983 b) Flow thresholds of functional and morphological damage of brain tissue. Stroke 14: 329–331

    PubMed  Google Scholar 

  14. Heiss WD, Rosner G (1983 c) Duration versus severity of ischemia as critical factors of cortical cell damage. In: Reivich M, Hurtig HI (eds) Cerebrovascular diseases. 13th Princeton conference on cerebrovascular disease. Raven New York, pp 225–236

    Google Scholar 

  15. Heiss WD (1992) Experimental evidence of ischemie thresholds and functional recovery. Stroke 23: 1668–1672

    PubMed  Google Scholar 

  16. Jin N, Parker CS, Roades RA (1991) Reactive oxygen-mediated contraction in pulmonary arterial smooth muscle: cellular mechanisms. Can J Physiol Pharmacol 69: 383–388

    PubMed  Google Scholar 

  17. Jorgensen MB, Deckert J, Wright DC (1989) Binding of [3H]phorbol 12,13-dibutyrate in rat hippocampus following transient global ischemia: a quantitative autoradiographic study. Neurosci Lett 103: 219–224

    PubMed  Google Scholar 

  18. Lassen NA, Vorstrup S (1984) Ischemie penumbra results in incomplete infarction: is the sleeping beauty dead? Stroke 15: 755

    PubMed  Google Scholar 

  19. Lin TN, Liu TH, Xu J, Hsu CY, Sun GY (1991) Brain polyphosphoinositide metabolism during focal ischemia in rat cortex. Stroke 22: 495–498

    PubMed  Google Scholar 

  20. Louis C, Magal E, Yavin E (1988) Protein kinase C alterations in fetal rat brain after global ischemia. J Biol Chem 263: 19282–19285

    PubMed  Google Scholar 

  21. Marcoux FW, Morawetz RB, Crowell RM, DeGirolami U, Halsey JH (1983) Regional vulnerability and selective necrosis in experimental focal cerebral ischemia. In: Reivich M, Huntig HI (eds) Cerebrovascular diseases. 13th Princeton conference on cerebrovascular disease. Raven, New York pp 213–223

    Google Scholar 

  22. Marcoux FW, Morawetz RB, Crowell RM, DeGirolami U, Halsey JH (1982) Differential regional vulnerability in transient focal cerebral ischemia. Stroke 13: 339–346

    PubMed  Google Scholar 

  23. Meyer FB, Sundt TH, Yanagihara T, Anderson RE (1987) Focal cerebral ischemia: pathophysiologic mechanisms and rationale for future avenues of treatment. Mayo Clin Proc 62: 35–55

    PubMed  Google Scholar 

  24. Morawetz RB, DeGirolami U, Ojemann RG (1978) Cerebral blood flow determinated by hydrogen clearance during middle cerebral artery occlusion in unanesthetized monkeys. Stroke 9: 143–149

    PubMed  Google Scholar 

  25. Onodera H, Araki T, Kogure K (1989) Protein kinase C activity in the rat hippocampus after forebrain ischemia: autoradiographic analysis by [3H]phorbol 12,13-dibutyrate. Brain Res 481: 1–7

    PubMed  Google Scholar 

  26. Onodera H, Kogure K (1989) Mapping second messenger systems in the rat hippocampus after transient forebrain ischemia: in vitro [3H]forskolin and [3H]inositol 1,4,5-trisphosphate binding. Brain Res 487: 343–349

    PubMed  Google Scholar 

  27. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 7th ed. Academic Press, New York

    Google Scholar 

  28. Sakurada O, Kennedy C, Jehle J, Brown JD, Carbin GL, Sokoloff L (1978) Measurement of local cerebral blood flow with iodo[14C]antipyrine. Am J Physiol 234: H59-H66

    PubMed  Google Scholar 

  29. Shimada N, Graf R, Rörner G, Wakayama A, Charles P, Heiss WD (1989) Ischemie flow threshold for extracellular glutamate increase in cat cortex. J Cereb Blood Flow Metab 9: 603–606

    PubMed  Google Scholar 

  30. Siesjo BK, Agardh CD, Bengtsson F (1989) Free radicals and brain damage. Cerebrovasc Brain Metab Rev 1: 165–211

    PubMed  Google Scholar 

  31. Tamura A, Asano T, Sano K (1980) Correlation between rCBF and histological changes following temporally middle cerebral artery occlusion. Stroke 11: 487–493

    PubMed  Google Scholar 

  32. Tamura A, Graham DI, McCulloch J, Teasdale GM (1981 a) Focal cerebral ischemia in the rat: 1. description of technique and early neuropathological consequences following middle cerebral artery occlusion. J Cereb Blood Flow Metab 1: 53–60

    PubMed  Google Scholar 

  33. Tamura A, Graham DI, McCulloch J, Teasdale GM (1981 b) Focal cerebral ischemia in the rat: 2. regional cerebral blood flow determined by [14C]Iodoantipyrine autoradiography following middle cerebral artery occlusion. J Cereb Blood Flow Metab 1: 61–69

    PubMed  Google Scholar 

  34. Tanaka K, Gotoh F, Gomi S, Takashima S, Mihara B (1991) Autoradiographic analysis on second-messenger systems and local cerebral blood flow in ischemie gerbil brain. J Cereb Blood Flow Metab 11: 283–291

    PubMed  Google Scholar 

  35. Tanaka K, Fukuuchi Y, Gomi S, Tanaka S, Mihara B, Shirai T, Nogawa S, Nozaki H, Nagata E (1992) Alteration of second-messenger ligand binding following 2-h hemispheric ischemia in the gerbil brain. Exp Neurol 117: 254–259

    PubMed  Google Scholar 

  36. Tenjin H, Ueda S, Mizukawa N, Imahori Y, Hino A, Ohmori Y, Yasukochi K, Wakita K, Horii H, Fujii R (1992) Positron emission tomographic measurement of acute hemodynamic change in primate middle cerebral artery occlusion. Neurol Med Chir (Tokyo) 32: 805–810

    Google Scholar 

  37. Tyson GW, Teasdale GM, Graham DI, McCulloch J (1984) Focal cerebral ischemia in the rat: topography of hemodynamic and histological changes. Ann Neurol 15: 539–567

    Google Scholar 

  38. Umemura A, Mabe H, Nagain H (1992 a) A phospholipase C inhibitor ameliorates postischemic neuronal damage in rats. Stroke 23: 1163–1166

    PubMed  Google Scholar 

  39. Umemura A, Mabe H, Nagai H, Sugino F (1992 b) Action of phospholipase A2 and C on free fatty acid release during complete ischemia in rat neocortex. J Neurosurg 76: 648–651

    PubMed  Google Scholar 

  40. Vacarrino F, Guidotti A, Costa E (1987) Ganglioside inhibition of glutamate-mediated protein kinase C translocation in primary cultures of cerebellar neurons. Proc Natl Acad Sci USA 84: 8707–8711

    PubMed  Google Scholar 

  41. Weiss S, Ellis J, Hendley DD, Lenox RH (1989) Translocation and activation of protein kinase C in striatal neurons in primary culture: relationship to phorbol dibutyrate actions on the inositol phosphate generating system and neurotransmitter. Neuro-chem 52: 530–536

    Google Scholar 

  42. Worley PF, Baraban JM, Snyder SH (1986) Heterogenous localization of protein kinase C in rat brain: autoradiographic analysis of phorbol ester receptor binding. J Neurosci 6: 199–207

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neuro-Isotope Laboratory and Cone Laboratory for Neurosurgical Research, Montreal Neurological Institute, Montreal, Quebec, Canada

    Y. L. Yamamoto & T. Nagao

  2. Department of Neurosurgery, Kumamoto University Medical School, Kumamoto, Japan

    N. Inoue, S. Goto, S. Nagahiro & Y. Ushio

Authors
  1. N. Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. L. Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Nagao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Goto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Nagahiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y. Ushio
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Inoue, N., Yamamoto, Y.L., Nagao, T. et al. Alterations of local cerebral blood flow, phorbol 12,13-dibutyrate binding activity, and histological damage during acute focal ischaemia in rat brain. Acta neurochir 138, 1118–1125 (1996). https://doi.org/10.1007/BF01412317

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01412317

Keywords

Search

Navigation