Skip to main content
SpringerLink
Log in

Cerebral ischemia in gerbils: Postischemic administration of cyclohexyl adenosine and 8-sulfophenyl-theophylline

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Adenosine agonists have now been shown by several laboratories to have profound neuroprotective effects when administered either pre-or postischemia. In an effort to determine whether these effects are centrally mediated, the effects of the non-brain-permeable aenosine receptor antagonist 8-sulfophenyl-theophylline (8-SPTH) on cyclohexyladenosine (CHA)-mediated protection was determined. Both survival and neurologic outcome were assessed in gerbils following 30 minutes of bilateral carotid occlusion. A dose of 2 mg/kg of CHA 5 minutes postreperfusion resulted in highly significant increases in survival relative to saline injected controls. Administration of doses of 8-SPTH sufficient to normalize the hypotension observed with CHA resulted in the same degree of postischemic protection. Similar results were obtained when neurologic status was evaluated. The results indicate that the neuroprotective effects of CHA are apparently centrally mediated.

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

  • Astrup, J., Sorensen, P.M., Sorensen, H.R. (1981). Oxygen and glucose consumption related to Na+−K+ transport in canine brain. Stroke 12:726–730

    PubMed  CAS  Google Scholar 

  • Brodie, M.S., Lee, K., Fredholm, B.B., Staahle, L., Dunwiddie, T.V. (1987). Central versus peripheral mediation of responses to adenosine receptor agonists: Evidence against a central mode of action. Brain Res. 415:323–330

    Article  PubMed  CAS  Google Scholar 

  • Burke, S.P., Nadler, J.V. (1988). Regulation of glutamate and aspartate release from slices of the hippocampal CA1 area: Effects of adenosine and baclofen. J. Neurochem. 51:154

    Article  Google Scholar 

  • Collis, M.G., Jacobson, K.A., Tomkins, D.M. (1987). Apparent affinity of some 8-phenyl-substituted xanthines at adenosine receptors in guinea-pig aorta and atria. Br. J. Pharmacol. 92:69–75

    PubMed  CAS  Google Scholar 

  • Daly, J.W. (1983). Role of ATP and adenosine receptors in physiologic process: Summary and prospects. Physiology and Pharmacology of Adenosine Derivatives. J.W. Daly, Y. Kuroda, J.W. Phillis, H. Shimizu, and M. Ui (eds). Raven Press, New York, pp 275–290

    Google Scholar 

  • Daval, J.-L., von Lubitz, D.K.J.E., Deckert, J., Redmond, D., Marangos, J.P. (1989). Protective effect of cyclohexyl adenosine on adenosine A1 receptors, guanine nucleotide and forskollin binding sites following transient brain ischemia: A quantitative autoradiographic study. Brain Res. 491:212–226

    Article  PubMed  CAS  Google Scholar 

  • DeLeo, J., Toth, L., Schubert, P., Rudolphi, K., Kreutzberg, G.W. (1987). Ischemia induced neuronal cell death, calcium accumulation, and glial response in the hippocampus of the Mongolian gerbil and protection by propentofylline (HWA 285). J. Cerebral Blood Flow Metab. 7:745–751

    CAS  Google Scholar 

  • DeLeo, J., Schubert, P., Kreutzberg, G.M. (1988). Propentofylline (HWA 285) protects hippocampal neurons of Mongolian gerbils against ischemic damage in the presence of an adenosine antagonist. Neurosci. Lett. 84:307–311

    Article  PubMed  CAS  Google Scholar 

  • Evans, M.C., Swan, J.H., Meldrum, B.S. (1987). An adenosine analogue, 2-chloroadenosine, protects against long term development of ischaemic cell loss in the rat hippocampus. Neurosci. Lett. 83:287–292

    Article  PubMed  CAS  Google Scholar 

  • Evoniuk, G., von Borstel, R.W., Wurtman, R.J. (1987). Antagonism of the cardiovascular effects of adenosine by caffeine or 8-(p-sulphophenyl)theophylline. J. Pharmacol. Exp. Ther. 2:428–432

    Google Scholar 

  • Foster, A.C., Gill, R., Iversen, L.L., Woodruff, G.N. (1987). Systemic administration of MK-801 protects against ischemia-induced hippocampal neurodegeneration in gerbils. Br. J. Pharmacol. Proc. Suppl. 90:9P

  • Gill, R., Foster, A.C., Woodruff, G.N. (1988). MK-801 is neuroprotective in gerbils when administered during the postischemic period. Neuroscience 25:847–855

    Article  PubMed  CAS  Google Scholar 

  • Ginsberg, M.D., Graham, D.I., Busto, R. (1985). Regional glucose utilisation and blood flow following graded forebrain ischemia in the rat: Carrelation with neuropathology. Ann. Neurol. 18:470–481

    Article  PubMed  CAS  Google Scholar 

  • Glanz, S.A. (1981). Primer of Biostatistics. McGraw-Hill, New York, pp 276–277

    Google Scholar 

  • Haller, Ch., Kuschinsky, W. (1987). Moderate hypoxia: Reactivity of pial arteries and local effect of theophylline. J. Appl. Physiol. 6:2208–2215

    Google Scholar 

  • Hossmann, K.-A. (1979). Cerebral dysfunction related to local and global ischemia of the brain. Brain Function in Old Age. F. Hoffmeister and C. Muller (eds). Springer-Verlag Berlin, pp 385–393

    Google Scholar 

  • Hossmann, K.-A., Lechtope-Gruter, H., Hossmann, V. (1973). The role of cerebral blood flow for the recovery of the brain after ischemia. Z. Neurol. 204:281–299

    Article  PubMed  CAS  Google Scholar 

  • Hossmann, K.-A., Sakaki, S., Kimoto, K. (1976). Cerebral uptake of glucose and oxygen in the cat brain after prolonged ischemia. Stroke 7:301–305

    CAS  Google Scholar 

  • Lawrence, J.J., Fuller, T.A., Olney, J.W. (1987). MK-801 and PCP protect against ischemic neuronal degeneration in the gerbil hippocampus. Soc. Neurosci. Abstr. 13:300.12

    Google Scholar 

  • Marangos, P.J., Boulenger, P.J. (1985). Basic and clinical aspects of adenosinergic neuromodulation. Neurosci. Biobehav. Rev. 9:421–430

    Article  PubMed  CAS  Google Scholar 

  • Marangos, P.J., von Lubitz, D.K.J.E., Daval, J.-L., Deckert, J. (1990). Adenosine: its relevance to the treatment of brain ischemia and trauma. Current and Future Trends in Anticonvulsant, Anxiety and Stroke Therapy. J. Emmet and M. Williams (eds). Alan R. Liss, New York, in press

    Google Scholar 

  • Michenfelder, J.D. (1974). The interdependency of cerebral functional and metabolic effects following massive doses of thiopental in the dog. Anesthesiology 41:231–236

    Article  PubMed  CAS  Google Scholar 

  • Miller, R.G. (1981). Survival Analysis. John Wiley & Sons, New York, pp 98–146

    Google Scholar 

  • Nowak, T.S., Jr. (1985) Synthesis of a stress protein following transient ischemia in the gerbils. J. Neurochem. 45:1635–1641

    Article  PubMed  CAS  Google Scholar 

  • Nowak, T.S., Jr. Fried, R.L., Lust, W.D., Passonneau, J.V. (1985). Changes in brain energy metabolism and protein synthesis following transient bilateral ischemia in the gerbil. J. Neurochem. 44:487–494

    Article  PubMed  CAS  Google Scholar 

  • Olney, J.M. (1987). Excitatory amino acids and neuropsychiatric disorders. Excitatory Amino Acid Transmission. T.P. Hicks, D. Lodge, and H. McLennan (eds). Alan R. Liss, New York, pp 217–224

    Google Scholar 

  • Olney, J.M., Labruyere, J., Price, M.T. (1989). Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science 244:1360–1362

    Article  PubMed  CAS  Google Scholar 

  • Phillis, J.W., Wu, P.H. (1981). The role of adenosine and its nucleotides in central synaptic transmission. Progr. Neurobiol. 16:187–239

    Article  CAS  Google Scholar 

  • Rehncrona, S., Abdul Rahman, A., Siesjo, B.K. (1973). Local cerebral blood flow in the postischemic period. Acta Neurol. Scand. 29:385–390

    Google Scholar 

  • Rosner, M.J. (1987). Cerebral perfusion pressure: Link between intracranial pressure and systemic circulation. Cerebral Blood Flow. J.H. Wood (ed). McGraw-Hill, New York, pp 425–448

    Google Scholar 

  • Rothman, S.M., Olney, J.W. (1986). Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Ann. Neurol. 19:105–111

    Article  PubMed  CAS  Google Scholar 

  • Rudolphi, K.A., Keil, M., Hinze, H.J. (1987). Effect of theophylline on ischemically-induced hippocampal damage in Mongolian gerbils: A behavioural and histopathological study. J. Cerebral Blood Flow Metab. 7:74–81

    CAS  Google Scholar 

  • Schmidt-Kastenr, R., Hossmann, K.-A., Grosse Ophoff, B. (1987). Pial artery pressure after one hour of global ischemia. J. Cerebral Blood Flow Metab. 7:109–117

    Google Scholar 

  • Strandgaard, S., Paulson, O.B. (1984). Cerebral autoregulation. Stroke 3:413–416

    Google Scholar 

  • Suzuki, R., Yamaguchi, T., Kirino, T., Orzi, F., Klatzo, I. (1983). The effects of 5-minute ischemia in Mongolian gerbils: I. Blood—brain barrier, cerebral blood flow, and local cerebral glucose utilization changes. Acta Neuropathol. (Berlin) 60:207–216

    Article  CAS  Google Scholar 

  • van Wylen, D.G.L., Park, T.S., Rubio, R., Berne, R.M. (1988). Cerebral blood flow and interstitial adenosine during hemorrhagic hypotension. Am. J. Physiol. 255 (Heart Circ. Physiol. 24):H1211-H1218

    PubMed  Google Scholar 

  • von Lubitz, D.K.J.E., Dambrosia, J.M., Kempsli, O., Redmond, D.J. (1988). Cyclohexyl adenosine protects against neuronal death following ischemia in the CA1 region of gerbil hippocampus. Stroke 19:1133–1139

    Google Scholar 

  • von Lubitz, D.K.J.E., Redmond, D.J. (1989). Cerebral ischemia in gerbils: Improvement of survival after postischemic treatment with oligo-prostaglandin B1. Eur. J. Pharmacol. 3:405–414

    Article  Google Scholar 

  • von Lubitz D.K.J.E., Dambrosia, J.M., Redmond, D.J. (1989). Protective effect of cyclohexyl adenosine in treatment of cerebral ischemia in gerbils. Neuroscience 2:451–462

    Google Scholar 

  • Weinberger, J., Nieves-Rosa, J. (1987). Cerebral blood flow in the evolution of infarction following unilateral carotid artery occlusion in Mongolian gerbil. Stroke 18:612–615

    PubMed  CAS  Google Scholar 

  • White, B.C., Wiegenstein, J.G., Wenegar, C.D. (1984). Brain ischemic anoxia. JAMA 12:1587–1590

    Google Scholar 

  • Winn, R.H., Rubio, R., Berne, R.M. (1981). The role of adenosine in the regulation of cerebral blood flow. J. Cerebral Blood Flow Metab. 1:239–244

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Gensia Pharmaceuticals, San Diego, California, USA

    Paul J. Marangos

  2. Department of Biochemistry, Hahnemann University School of Medicine, 19102, Philadelphia, PA, USA

    Dag K. J. E. von Lubitz

Authors
  1. Dag K. J. E. von Lubitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul J. Marangos
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Office of Naval Research Contract NOOO14-86-K-0471 sponsored parts of this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

von Lubitz, D.K.J.E., Marangos, P.J. Cerebral ischemia in gerbils: Postischemic administration of cyclohexyl adenosine and 8-sulfophenyl-theophylline. J Mol Neurosci 2, 53–59 (1990). https://doi.org/10.1007/BF02896926

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02896926

Keywords

Search

Navigation