Self-Defense of the Brain: Adenosinergic Strategies in Neurodegeneration

  • K. J. Dag
  • E. von Lubitz
  • Paul J. Marangos
Part of the Advances in Neuroprotection book series (AN, volume 22)


Despite steady progress in their diagnosis and treatment, the disorders of the central nervous system (CNS) still remain a great challenge to modern medicine. The breadth and scope of the pathologic factors are such that, even with the improved understanding of the involved events, it is extremely difficult to decide which of them are the primary instigators of the ensuing damage and which are but secondary effects of an ongoing process of the neuronal destruction. The most striking example of the magnitude of the problems that must be faced is provided by the diseases that affect the supply of blood to the brain.


Cerebral Ischemia Adenosine Receptor Cereb Blood Flow Forebrain Ischemia Extracellular Adenosine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abe K, Kogure K, Yamamoto H, Imazawa M, Miyamoto K (1987): Mechanism of arachidonic acid liberation during ischemia in gerbil cerebral cortex. JNeurochem 48: 503Google Scholar
  2. Alexander SP, Reddington M (1989): The cellular localization of adenosine receptors in rat neostriatum. Neuroscience 3: 645–651Google Scholar
  3. Ames, A III, Wright RL, Kowada M, Thurston JM, Majno G (1968): The no-reflow phenomenon. Am J Pathol 52: 437–453PubMedPubMedCentralGoogle Scholar
  4. Arch JRS, Newsholme EA (1978): The control of metabolism and the hormonal role of adenosine. Essays Biochem 14: 82–121PubMedGoogle Scholar
  5. Attwell D, Sarantis M, Szatkowski M, Barbour B, Brew H (in press) In: Excitatory Amino Acids and Synaptic Function,Wheal A, Thomson A, eds. Academic PressGoogle Scholar
  6. Ault B, Wang CM (1986): Adenosine inhibits epileptiform activity arising in hippocampal area CA3. Br J Pharmacol 87: 695–703PubMedPubMedCentralGoogle Scholar
  7. Barbour, B, Szatkowski M, Ingledew N, Attwell D (1989): Arachidonic acid induces a prolonged inhibition of glutamate uptake into glial cells. Nature 342: 918–920ADSPubMedGoogle Scholar
  8. Barraco RA, Swanson RH, Phillis JW, Berman RF (1984): Anticonvulsant effects of adenosine analogues on amygdaloid-kindled seizures in rats. Neurosci Lett 46: 317–322PubMedGoogle Scholar
  9. Barraco RA, Bryant ShD (1987): Depression of locomotor activity following bilateral injections of adenosine into the striatum of mice. Med Sci Res 15: 421–422Google Scholar
  10. Bartrup JT, Stone TW (1988): Presynaptic actions of adenosine are magnesium dependent. Neuropharmacology 7: 761–763Google Scholar
  11. Bartus RT (1990): Drugs to treat age-related neurodegenerative problems: The final frontier of medical science? J Am Geriatr Soc 38: 680–695PubMedGoogle Scholar
  12. Beneveniste H, Drejer J, Schousboe A, Diemer NH (1984): Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem 43: 1369–1374Google Scholar
  13. Bengtsson F, Siesjö BK (1990): Cell damage in cerebral ischemia: Physiological and structural aspects. In: Cerebral Ischemia and Resuscitation, Schurr A, Rigor, BM, eds. Boca Raton, Florida: CRC PressGoogle Scholar
  14. Benzinger M (1969): Tympanic thermometry in surgery and anesthesia. JAMA 8: 1207–1211Google Scholar
  15. Berne RM, Rubio R, Curnish RR (1974a): Release of adenosine from ischemic brain. Circ Res 35: 263–271Google Scholar
  16. Berne RM, Rubio R, Curnish RR (1974b): Release of adenosine from ischemic brain: Effect on vascular resistance and incorporation into cerebral adenine nucleotides. Circ Res 35: 262–271Google Scholar
  17. Bernstein M, Fleming JF, Deck JH (1984): Cerebral hypoperfusion after carotid endarterectomy: A cause of cerebral hemorrhage. Neurosurgery 15: 50–56PubMedGoogle Scholar
  18. Boarini DJ, Kassel NF, Sprowell JR, Olin J (1984): Intravertebral adenosine fails to alter cerebral blood flow in the dog. Stroke 15: 1057–1060PubMedGoogle Scholar
  19. Brodie MS, Lee KS, Fredholm BB, Stahle L, Dunwiddie TV (1987): Central versus peripheral mediation of responses to adenosine receptor agonists: Evidence against a central mode of action. Brain Res 415: 323–330PubMedGoogle Scholar
  20. Bruns RF, Katims JJ, Annaus Z, Snyder SH, Daly JW (1983): Adenosine receptor interactions and anxiolytics. Neuropharmacology 12B: 1523–1529Google Scholar
  21. Burke SP, Nadler JV (1988): Regulation of glutamate and aspartate release from slices of the hippocampal CA1 area: Effects of adenosine and baclofen. J Neurochem 51: 1541–1551PubMedGoogle Scholar
  22. Burnstock G (1981): Neurotransmitters and trophic factors in the autonomic nervous system. J Physiol (Loud) 313: 1–35Google Scholar
  23. Busto R, Harik SI, Yoshida S, Scheinberg P, Ginsberg MD (1985): Cerebral norepinephrine depletion enhances recovery after brain ischemia. Ann Neurol 18: 329–336PubMedGoogle Scholar
  24. Busto R, Dietrich WD, Globus M-YT, Valdes I, Scheinberg P, Ginsberg MD (1987): Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab 7: 729–738Google Scholar
  25. Busto R, Dietrich WD, Globus, M-YT, Ginsberg MD (1989): Postischemic moderate hypothermia inhibits CA1 hippocampal ischemic neuronal injury. Neurosci Lett 101: 299–304PubMedGoogle Scholar
  26. Cantu RC, Ames A III (1969): Distribution of vascular lesions caused by cerebral ischemia. Relation to survival. Neurology 19: 128–132PubMedGoogle Scholar
  27. Chan PH, Fishman RA, Chen SF, Chew S (1983): Effects of temperature on arachidonic acid-induced cellular edema and membrane perturbation in rat brain cortical slices. J Neurochem 41: 1550–1557PubMedGoogle Scholar
  28. Chan PH (1988): The role of oxygen radicals in brain injury and edema. In: Cellular Antioxidant Defense Mechanisms, Chow CK, ed., Vol. III. Boca Raton, Florida: CRC PressGoogle Scholar
  29. Chan PH, Fishman RA, Schmiedley JW, Chen SF (1984): Release of polyunsaturated fatty acids from phospholipids and alteration of brain membrane by oxygen-derived free radicals. J Neurosci Res 12: 595–605PubMedGoogle Scholar
  30. Choi DW (1988): Glutamate neurotoxicity and diseases of the nervous system. Neuron 1: 623–634Google Scholar
  31. Choi DW (1990): Methods for antagonizing glutamate neurotoxicity. Cerebrovasc Brain Metab 2: 105–147Google Scholar
  32. Coffin VL, Carney JM (1986): Effects of selected analogs of adenosine on schedule-controlled behavior in rats. Neuropharmacology 25: 1141–1147PubMedGoogle Scholar
  33. Cord JM (1985): Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 312: 159–163Google Scholar
  34. Crawley JN, Patel J, Marangos JP (1983): Adenosine uptake inhibitors potentiate the sedative effects of adenosine. Neurosci Lett 36: 169–174PubMedGoogle Scholar
  35. Cronstein BN, Levin RI, Belanoff J, Weissman G, Hirschhorn R (1986): Adenosine: An endogenous inhibitor of neutrophil-mediated injury to endothelial cells. J Clin Invest 78: 769–770Google Scholar
  36. Daly JW, Bruns RF, Snyder SH (1981): Adenosine receptors in the central nervous system: Relationship to the central actions of methylxanthines. Life Sci 28: 2083–2097PubMedGoogle Scholar
  37. Daval, J-L, von Lubitz DKJE, Deckert J, Redmond DJ, Marangos PJ (1989): Protective effect of cyclohexyladenosine on adenosine Al receptors, guanine nucleotide and forskolin binding sites following transient brain ischemia: A quantitative autoradiographic study. Brain Res 491: 212–226PubMedGoogle Scholar
  38. DeLeo J, Toth L, Schubert P, Rudolphi K, Kreutzberg GW (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 Cereb Blood Flow Metab 7: 745–751PubMedGoogle Scholar
  39. DeLeo J, Schubert P, Kreutzberg GW (1988a): Propentofylline (HWA 285) protects hippocampal neurons of Mongolian gerbils against ischemic damage in the presence of an adenosine antagonist. Neurosci Lett 84: 307–311PubMedGoogle Scholar
  40. DeLeo J, Schubert P, Kreutzberg GW (1988b): Protection against ischemic brain damage using propentofylline in gerbils. Stroke 19: 1535–1539PubMedGoogle Scholar
  41. Demopoulos HB, Flamm ES, Seligman ML, Mitamura JA, Ransohoff J (1979): Membrane perturbations in the central nervous system injury: Theoretical basis for free radical damage and a review of the experimental data. In: Neural Trauma, Popp AJ, ed. New York: Raven PressGoogle Scholar
  42. Dolphin AC, Prestwich SA (1985): Pertussis toxin reverses adenosine inhibition of neuronal glutamate release. Nature 316: 148–150ADSPubMedGoogle Scholar
  43. Dora E (1986): Effect of theophylline on the functional hyperaemic and hypoxic responses of cerebrocortical microcirculation. Acta Physiol Hung 68: 183–197PubMedGoogle Scholar
  44. Drury AN, Szent-Györgyi A (1929): The physiological activity of adenosine compounds with especial reference to their action upon mammalian heart. J Physiol (Lond) 68: 213–237Google Scholar
  45. Duncan MJ, Morgan PF (1989): NECA-induced hypomotility in mice: Evidence for a predominantly central site of action. Pharmacol Biochem Behav 32: 487–490Google Scholar
  46. Dunwiddie TV (1980): Endogenously released adenosine regulates excitability in the in vitro hippocampus. Epilepsia 21: 541–548PubMedGoogle Scholar
  47. Dunwiddie TV, Fredholm BB (1984): Adenosine receptors mediating inhibitory electrophysiological responses in rat hippocampus are different from receptors mediating cyclic AMP accumulation. Naunyn-Schmiedbergs Arch. Pharmacol 326: 294–301Google Scholar
  48. Dunwiddie TV (1984): Interactions between the effects of adenosine and calcium on synaptic responses in rat hippocampus in vitro. J Physiol (Lond) 350: 545–559Google Scholar
  49. Dunwiddie TV (1985): The physiological role of adenosine in the central nervous system. Int Rev Neurobiol 27: 64–139Google Scholar
  50. Edvinson L, Fredholm BB (1983): Characterization of adenosine receptors in isolated cerebral arteries of cat. Br J Pharmacol 80: 631–637Google Scholar
  51. Emerson TE, Raymond RM (1981): Involvement of adenosine in cerebral hypoxic hyperemia in the dog. Am J Physiol 241: H134–138PubMedGoogle Scholar
  52. Engler R (1987): Consequences of activation and adenosine-mediated inhibition of granulocytes during myocardial ischemia. Fed Proc 46: 2407–2412PubMedGoogle Scholar
  53. Erecinska M, Nelson D, Wilson DF, Silver IA (1984): Neurotransmitter amino acids in the CNS. I. Regional changes in amino acid levels in rat brain during ischemia and reperfusion. Brain Res 304: 9–22PubMedGoogle Scholar
  54. Evans MC, Swan JH, Meldrum BS (1987): An adenosine analogue, 2-chloroadenosine, protects against long term development of ischemic cell loss in the rat hippocampus. Neurosci Lett 83: 287–292PubMedGoogle Scholar
  55. Evoniuk G, von Borstel RW, Wurtman RJ (1987): Antagonism of cardiovascular effects of adenosine by caffeine or 8-(p-sulfophenyl)theophylline. J Pharmacol Exp Ther 2: 428–432Google Scholar
  56. Fischer EG, Ames A III (1972): Studies on impairment of cerebral circulation following ischemia: Effect of hemodilution and perfusion pressure. Stroke 3: 538–542PubMedGoogle Scholar
  57. Fredholm BB, Dunwiddie TV (1988): How does adenosine inhibit transmitter release. Trends Pharmacol Sci 9: 130–134PubMedGoogle Scholar
  58. Fujimoto T, Suzuki H, Tanoue K, Fukushima Y, Yamazaki H (1985): Cerebrovascular injuries and brain edema following activation of platelets. In: Brain Edema, 4th Int. Symp. on Brain Edema, Tokyo 1984, Inaba Y, Klatzo I, Spatz M, eds. Berlin: Springer-VerlagGoogle Scholar
  59. Geiger JD (1986): Localization of [3H]cyclohexyladenosine and [3H]nitrobenzylthioinosine binding sites in rat striatum and superior colliculus. Brain Res 36: 404–408Google Scholar
  60. Ginsberg MD (1990): Local metabolic responses to cerebral ischemia. Cerebrovasc Brain Metab 2: 58–93Google Scholar
  61. Globus MY-T, Busto R, Dietrich D, Martinez E, Valdes I, Ginsberg MD (1988): Intra-ischemic extracellular release of dopamine and glutamate is associated with striatal vulnerability to ischemia. Neurosci Lett 91: 36–40PubMedGoogle Scholar
  62. Glowa JR, Spealman RD (1984): Behavioral effects of caffeine, N6-(L-phenylisopropyl)adenosine and their combination in the squirrel monkey. JPharmacol Exp Ther 216: 484–491Google Scholar
  63. Goldstein M (1990): Decade of the brain: Challenge and opportunities in stroke research. Stroke 3: 373–374Google Scholar
  64. Goodman RR, Cooper MJ, Gavish M, Snyder SH (1981): Guanine nucleotide and cation regulation of the binding of [3H]cyclohexyladenosine and [3H]diethylphenylxanthine to adenosine Al receptors in brain membranes. Mol Pharmacol 21: 329–335Google Scholar
  65. Grenmyre TJ, Young AB (1989): Excitatory amino acids and Alzheimer’s disease. Neurobiol Aging 10: 593–602Google Scholar
  66. Haas HL, Greene RW (1984): Adenosine enhances afterhyperpolarization and accommodation in hippocampal pyramidal cells. Pflugers Arch 402: 244–247PubMedGoogle Scholar
  67. Hagberg H, Andersson P, Lazarewicz J, Jacobson I, Butcher S, Sandberg M (1987): Extracellular adenosine, inosine, hypoxanthine, and xanthine in relation to tissue nucleotides in rat striatum during transient ischemia. J Neurochem 49: 227–335PubMedGoogle Scholar
  68. Hagberg H, Andine P, Lehmann A (1990): Excitatory amino acids and hypoxicischemic damage in the immature brain. In: Cerebral Ischemia and Resuscitation, Schurr A, Rigor, BM, eds. Boca Raton, Florida: CRC PressGoogle Scholar
  69. Haller C, Kuschinsky W (1987): Moderate hypoxia: Reactivity of pial arteries and local effect of theophylline. J Appl Physiol 63: 2208–2215PubMedGoogle Scholar
  70. Handa J, Kidooka M, Takenaka T (1990): Calcium and free fatty acids in cerebral ischemic cell damage. In: Cerebral Ischemia and Resuscitation, Schurr A, Rigor, BM, eds. Boca Raton, Florida: CRC PressGoogle Scholar
  71. Hansen AJ (1985): Effect of anoxia on ion distribution in the brain. Physiol Rev 65: 101–145PubMedGoogle Scholar
  72. Hansen AJ (1990): Ion homeostasis in cerebral ischemia. In: Cerebral Ischemia and Resuscitation, Schurr A, Rigor, BM, eds. Boca Raton, Florida: CRC PressGoogle Scholar
  73. Harms HH, Wardeh G, Mulder AH (1979): Effects of adenosine on depolarization-induced release of various radiolabeled neurotransmitters from slices of rat corpus striatum. Neuropharmacology 18: 577–580PubMedGoogle Scholar
  74. Heistad DD, Marcus ML, Gourley JK, Busija DW (1981): Effect of adenosine and dipyridamole on cerebral blood flow. Am J Physiol 240: H775–780PubMedGoogle Scholar
  75. Hillered L, Smith M-L, Siesjö BK (1985): Lactic acidosis and recovery of the mitochondrial function following forebrain ischemia in rat. J Cereb Blood Flow Metab 5: 259–266PubMedGoogle Scholar
  76. Hoffman BB, Dall’aglio E, Hollenbeck C, Chang H, Reaven GM (1986): Suppression of free fatty acids and triglycerides in normal and hypertriglycemic rats by the adenosine receptor agonist phenylisoprophyladenosine. J Pharmacol Exp Ther 3: 715–718Google Scholar
  77. Hoffman WE, Albrecht RF, Miletich DJ (1984): The role of adenosine in CBF increases during hypoxia in young vs. aged rats. Stroke 15: 124–129PubMedGoogle Scholar
  78. Holton FA, Holton P (1954): The capillary dilator substances in dry powder of spinal roots: A possible role of adenosine triphosphate in chemical transmission from nerve endings. J Physiol (Loud) 126: 124–140Google Scholar
  79. Hossman K-A, Lechapte Gruter H, Hossman V (1973): The role of cerebral blood flow for the recovery of the brain after prolonged ischemia. Z Neurol 204: 281–299Google Scholar
  80. Hossman K-A, Sakaki S, Kimoto K (1976): Cerebral uptake of glucose and oxygen in the cat brain after prolonged ischemia. Stroke 7: 301–305Google Scholar
  81. Hyman TB, Van Hoesen GW, Damasio AR (1987): Alzheimer’s disease: Glutamate depletion in the hippocampal perforant pathway zone. Ann Neurol 22: 37–40PubMedGoogle Scholar
  82. Ikeda J, Nagashima G, Saito N, Nowak TS, Joo F, Mies G, Lohr JM, Ruetzler ChA, Klatzo I (1990): Putative neuroexcitation in cerebral ischemia and brain injury. Stroke 21 (Suppl III): 65–70Google Scholar
  83. Itoh T, Kawakami M, Yamaguchi Y (1986): Effect of allopurinol on ischemia and reperfusion induced cerebral injury in spontaneously hypertensive rats. Stroke 17: 1284–1287PubMedGoogle Scholar
  84. Jörgensen MB, Johansen FF, Diemer NH (1987): Removal of entorhinal cortex protects CA 1 neurons from ischemic damage. Acta Neuropathol (Berl) 60: 217–222Google Scholar
  85. Kagström E, Smith M-L, Siesjö BK (1983): Recirculation in the rat following incomplete ischemia. J Cereb Blood Flow Metab 3: 183–192PubMedGoogle Scholar
  86. Kalimo H, Olsson Y, Paljarvi L, Söderfeldt B (1982): Structural changes in brain tissue under hypoxic-ischemic conditions. J Cereb Blood Flow Metab 2 (Suppl 1): S19 - S23PubMedGoogle Scholar
  87. Kirino T (1982): Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239: 257–269Google Scholar
  88. Kirino T, Sano K (1984): Selective vulnerability in the gerbil hippocampus following transient ischemia. Acta Neuropathol (Berl) 62: 201–208Google Scholar
  89. Kontos HA (1989): Oxygen radicals in cerebral ischemia. In: Cerebrovascular Diseases, 16th Princeton Conf., Ginsberg MD, Dietrich WD, eds. New York: Raven PressGoogle Scholar
  90. Kraft SA, Larson CP Jr, Shuer LM, Steinberg G, Benson GV, Pearl RG (1990): Effect of hyperglycemia on neuronal changes in a rabbit model of focal cerebral ischemia. Stroke 21: 447–450PubMedGoogle Scholar
  91. Kreutzberg GW, Barron KD, Schubert P (1978): Cytochemical localization of 5-nucleotidase in glial plasma membranes. Brain Res 158: 247–257PubMedGoogle Scholar
  92. Krieglstein J (1990): Pharmacology and drug therapy of Cerebral ischemia. In: Cerebral Ischemia and Resuscitation, Schurr A, Rigor, BM, eds. Boca Raton, Florida: CRC PressGoogle Scholar
  93. Krnjevic K (1990): Adenosine triphosphate-sensitive potassium channels in anoxia. Stroke 21 (Suppl III): 190–193Google Scholar
  94. Kukovetz WR, Poch G, Holzman S, Wurm A, Rinner I (1978): Role of cyclic nucleotides in adenosine mediated regulation of coronary flow. Adv Cyclic Nucleotide Res 9: 397–409PubMedGoogle Scholar
  95. Laham A, Claperon N, Durussel JJ, Fattal E Delattre J, Pusieux F, Couvreur P, Rossignol P (1987): Liposomally-entrapped ATP: Improved efficiency against experimental brain ischemia in the rat. Life Sci 40: 2011–2016PubMedGoogle Scholar
  96. Lassen NA (1959): Cerebral blood flow and oxygen consumption in man. Physiol Rev 39: 183–238PubMedGoogle Scholar
  97. Lee KS, Reddington M, Schubert P, Kreutzberg GW (1983): Regulation of the strength of adenosine modulation in the hippocampus by a differential distribution of the density of Al receptors. Brain Res 260: 156–159PubMedGoogle Scholar
  98. Lee KS, Schubert P, Reddington M, Kreutzberg GW (1986a): The distribution of adenosine receptors and 5-nucleotidase in the hippocampal formation of several mammalian species. J Comp Neurol 246: 427–434PubMedGoogle Scholar
  99. Lee KS, Tetzlaff W, Kreutzberg GW (1986b): Rapid down-regulation of hippo-campal adenosine receptors following brief anoxia. Brain Res 380: 155–158PubMedGoogle Scholar
  100. Lee KS, Reddington M (1986): Autoradiographic evidence for multiple CNS binding sites for adenosine derivatives. Neuroscience 2: 535–549Google Scholar
  101. Long JB, Rigamonti DD, Martinez-Arizala A (1989): The adenosine analogs 2-chloroadenosine (2CA) and 5-(N-ethyl)carboxamidoadenosine (NECA) protect against dynorphin A (DYN)-induced rat spinal cord injury. Soc Neurosci Abstr 15 (1): 42Google Scholar
  102. Madison DV, Fox AP, Tsien RW (1987): Adenosine reduces an inactivating component of calcium current in hippocampal CA3. Biophys J 51 (abstr): 30AGoogle Scholar
  103. Marangos PJ, Bouleneger JP (1985): Basic and clinical aspects of adenosinergic neuromodulation. Neurosci Biobehav Rev 9: 421–430PubMedGoogle Scholar
  104. Marangos PJ, von Lubitz DKJE, Daval J-L, Deckert J (1990): Adenosine: Its relevance to the treatment of brain ischemia and trauma. In: Current and Future Trends in Anticonvulsant, Anxiety, and Stroke Therapy, Meldrum BS, Williams M, eds. Baltimore: Wiley-Liss, Inc.Google Scholar
  105. Marcum JM, Dedman JR, Brinkley BR, Means A (1978): Control of microtubule assembly-disassembly by calcium dependent regulator protein. Proc. Natl. Acad. Sci. USA Google Scholar
  106. Mayer ML, Westbrook GL, Guthrie PB (1984): Voltage dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature 309: 261–263ADSPubMedGoogle Scholar
  107. Mayer ML, Westbrook GL (1987): Cellular mechanisms underlying neurotoxicity. Trends Neurosci 2: 59–61Google Scholar
  108. McAfee DA, Henon BK (1985): Adenosine and ATP. In: Neurotransmitter Actions in the Vertebrate Nervous System, Rogawski MA, Barker JL, eds. New York: Plenum PressGoogle Scholar
  109. McBean DE, Harper AM, Rudolphi KA (1988): Effects of adenosine and its analogues on porcine basilar arteries: Are only A2 receptors involved? J Cereb Blood Flow Metab 8: 40–45PubMedGoogle Scholar
  110. Minamisawa H, Mellergard P, Smith M-L, Bengtsson F, Theander S, Boris-Möller F, Siesjö BK (1990): Preservation of brain temperature during ischemia in rats. Stroke 21: 758–764PubMedGoogle Scholar
  111. Morii S, Ngai AC, Ko KR, Winn HR (1987): Role of adenosine in regulation of cerebral blood flow: Effect of theophylline during normoxia and hypoxia. Am J Physiol 253: H165–175PubMedGoogle Scholar
  112. Murray TF, Cheney DL (1982): Neuronal location of N6-cyclohexyl[3H]adenosine binding sites in rat and guinea-pig brain. Neuropharmacology 24: 575–580Google Scholar
  113. Murray TF, Sylvester D, Schultz CS, Szot P (1985): Purinergic modulation of the seizure threshold for pentylentetrazol in the rat. Neuropharmacology 8: 761–766Google Scholar
  114. Myers RE (1979): Lactic acid accumulation as a cause of brain edema and cerebral necrosis resulting from oxygen deprivation. In: Advances in Perinatal Neurology, Korobkin R, Guilleminault G, eds. New York: SpectrumGoogle Scholar
  115. Nedergaard M, Diemer N (1987): Focal ischemia of the rat brain, with special reference to the influence of plasma glucose concentration. Acta Neuropathol (Berl) 73: 131–137Google Scholar
  116. Nedergaard M (1988): Mechanisms of brain damage in focal cerebral ischemia. Acta Neurol Scand 77: 81–101PubMedGoogle Scholar
  117. Newby AC (1984): Adenosine as a retaliatory metabolite. Trends Biol Sci 9: 42–44Google Scholar
  118. Nicholls DG (1989): Release of glutamate, aspartate and -y-aminobutyric acid from isolated nerve terminals. J Neurochem 2: 331–341Google Scholar
  119. Nicholls D, Attwell D (1990): The release and uptake of excitatory amino acids. Trends Pharmacol Sci 11: 462–468Google Scholar
  120. Novak L, Bregestovski P, Ascher P, Herbert A, Prochiantz A (1985): Magnesium gates glutamate activated channels in mouse central neurones. Nature 316: 440ADSGoogle Scholar
  121. Olesen SP (1987): Free oxygen radicals decrease electrical resistance of microvas-cular endothelium in brain. Acta Physiol Scand 129: 181–187PubMedGoogle Scholar
  122. Onodera H, Kogure K (1985): Autoradiographic visualization of adenosine Al receptors in the gerbil hippocampus: Changes in the receptor density after transient ischemia. Brain Res 345: 406–408PubMedGoogle Scholar
  123. Onodera H, Kogure K (1990): Calcium antagonist, adenosine Al and muscarine bindings in rat hippocampus after transient ischemia. Stroke 21: 771–776PubMedGoogle Scholar
  124. Patt A, Harkem AH, Burton LK, et al. (1988): Xanthine oxidase-derived hydrogen peroxide contributes to ischemia-reperfusion edema in gerbil brains. Ann Neurol 81: 1556–1562Google Scholar
  125. Phillis JW, Wu PH (1981): The role of adenosine and its nucleotides in central synaptic transmission. Progr Neurobiol 16: 187–239Google Scholar
  126. Phillis JW, Wu PH (1983): The role of adenosine in central neuromodulation. In: Regulatory Function of Adenosine, Berne RM, Rall TW, Rubio R eds. Boston: NijhoffGoogle Scholar
  127. Phillis JW, O’Regan MH, Walter GA (1988): Effects of nifedipine and felodipine on adenosine and inosine release from the hypoxemic rat cerebral cortex. J Cereb Blood Flow Metab 8: 179–185PubMedGoogle Scholar
  128. Phillis JW, O’Regan MH (1988): Deoxycoformycin prevents ischemia-induced locomotor hyperactivity in the unanesthetized gerbil. Med Sci Res 16: 897–898Google Scholar
  129. Phillis JW, O’Regan M (1989): Deoxycoformycin antagonizes ischemia-induced neuronal degeneration. Brain Res Bull 22: 537–540PubMedGoogle Scholar
  130. Phillis JW (1989): Xanthine oxidase inhibition attenuates ischemic brain injury in the gerbil. Med Sci Res 17: 137–138ADSGoogle Scholar
  131. Phillis JW (1990a): Adenosine, inosine, and the oxypurines in cerebral ischemia. In: Cerebral Ischemia and Resuscitation, Schurr A, Rigor, BM, eds. Boca Raton, Florida: CRC PressGoogle Scholar
  132. Phillis JW (1990b): Adenosine in the control of the cerebral circulation. Cerebrovasc Brain Metab 1: 26–54Google Scholar
  133. Poulson OB, Strandgard S, Edvinsson L (1990): Cerebral autoregulation. Cerebrovasc Brain Metab 2: 161–192Google Scholar
  134. Prestwich SA, Forda SR, Dolphin AC (1987): Adenosine antagonists increase spontaneous and evoked transmitter release from neuronal cells in culture. Brain Res 405: 130–139PubMedGoogle Scholar
  135. Pulsinelli WA, Levy DE, Duffy E (1982): Regional cerebral blood flow and glucose metabolism following transient forebrain ischemia. Ann Neurol 11: 499–509PubMedGoogle Scholar
  136. Rehncrona S, Siesjö BK, Westerberg E (1978): Adenosine and cyclic AMP in cerebral cortex of rats in hypoxia, status epilepticus and hypercapnia. Acta Physiol Scand 104: 453PubMedGoogle Scholar
  137. Ribeiro JA, Sebastiao AM (1988): Subtypes of adenosine receptors. Trends Pharmacol Sci 9: 279–280PubMedGoogle Scholar
  138. Rosenthal R, Fiskum G (1990): Brain mitochondrial function in cerebral ischemia and resuscitation. In: Cerebral Ischemia and Resuscitation, Schurr A, Rigor, BM, eds. Boca Raton, Florida: CRC PressGoogle Scholar
  139. Rosner MJ (1987): Cerebral perfusion pressure: Link between intracranial pressure and systemic circulation. In: Cerebral Blood Flow, Wood JH, ed. New York: McGraw-HillGoogle Scholar
  140. Rothman SM, Olney JW (1986): Glutamate and the pathophysiology of hypoxicischemic brain damage. Ann Neurol 19: 105–111PubMedPubMedCentralGoogle Scholar
  141. Rudolphi KA, Keil M, Hinze H-J (1987): Effect of theophylline on ischemically induced hippocampal damage in Mongolian gerbils: A behavioural and histopathological study. J Cereb Blood Flow Metab 7: 74–81PubMedGoogle Scholar
  142. Safar P (1988): Resuscitation from clinical death: Pathophysiologic limits and therapeutic potentials. Crit Care Med 16: 923–941PubMedGoogle Scholar
  143. Schlaepfer WW, Zimmerman U-JP, Micko S (1981): Neurofilament proteolysis in rat peripheral nerve: Homologies with calcium-activated proteolysis in other tissues. Cell Calcium 2: 235–250Google Scholar
  144. Schmidt-Kastner R, Hossman K-A, Grosse Ophoff B (1987): Pial artery pressure after one hour global ischemia. J Cerebr Blood Flow Metab 7: 74–8111Google Scholar
  145. Schmiedley JW (1990): Free radicals in central nervous system ischemia. Stroke 7: 1086–1090Google Scholar
  146. Schubert P, Dux E (1990): Selective neuronal death in cerebral ischemia and protective mechanisms. In: Cerebral Ischemia and Resuscitation, Schurr A, Rigor, BM, eds. Boca Raton, Florida: CRC PressGoogle Scholar
  147. Schubert P, Dux E (1990): Selective neuronal death in cerebral ischemia and protective mechanisms. In: Cerebral Ischemia and Resuscitation, Schurr A, Rigor, BM, eds. Boca Raton, Florida: CRC PressGoogle Scholar
  148. Schuldiner S (1987): Role of neurotransmitter transport processes in synaptic transmission. CRC Crit Rev Biochem 22: 1–38PubMedGoogle Scholar
  149. Segal M (1982): Intracellular analysis of a postsynaptic action of adenosine in the rat hippocampus. Eur J Pharmacol 79: 193–199PubMedGoogle Scholar
  150. Seida M, Wagner HG, Vass K, Klatzo I (1988): Effect of aminophylline on postischemic edema and brain damage in cats. Stroke 19: 1275–1282PubMedGoogle Scholar
  151. Siesjö BK (1981): Cell damage in the brain: A speculative synthesis. J Cereb Blood Flow Metab 1: 155–185Google Scholar
  152. Siesjö BK, Wieloch T (1985): Cerebral metabolism in ischemia: Neurochemical basis for therapy. Br . J. Anesth. 57: 47–62Google Scholar
  153. Siesjö BK (1988a): Historical overview: Calcium, ischemia and death of brain cells. Ann NY Acad Sci 522: 638–661ADSPubMedGoogle Scholar
  154. Siesjö BK (1988b): Mechanisms of ischemic brain damage. Crit. Care Med 16: 954–963PubMedGoogle Scholar
  155. Siesjö BK, Bengtsson F (1989a): Calcium fluxes, calcium antagonists, and calcium-related pathology in brain ischemia, hypoglycemia, and spreading depression: A unifying hypothesis. J Cereb Blood Flow Metab 9: 127–140Google Scholar
  156. Siesjö BK, Bengtsson F (1989b): Calcium, calcium antagonists and ischemic cell death in the brain. In: Pharmacology of Cerebral Ischemia, Proc 2nd Int. Symp on Pharmacology of Cerebral Ischemia, Marburg 1988, J Krieglstein, ed. Boca Raton, Florida: CRC PressGoogle Scholar
  157. Siesjö BK, Agardh C-D, Bengtsson F (1990a): Free radicals and brain damage. Cerebrovasc Brain Metab 1: 165–211Google Scholar
  158. Siesjö BK, Ekholm A, Kenichiro K, Theander S (1990b): Acid-base changes during complete brain ischemia. Stroke 21 (Suppl III): 193–199Google Scholar
  159. Sollevi A, Torssell L, Fredholm BB, Stettergren G, Blomback M (1985): Adenosine spares platelets during cardiopulmonary bypassing in man without causing systemic vasodilation. Scand J Thorac Surg 19: 155–159Google Scholar
  160. Sollevi A (1986): Cardiovascular effects of adenosine in man: Possible clinical implications. Progr Neurobiol 27: 319–349Google Scholar
  161. Smith M-L, von Hanwehr R, Siesjö BK (1986): Changes in extra-and intracellular pH in the brain during and following ischemia in hyperglycemic and moderately hypoglycemic rats. J Cereb Blood Flow Metab 5: 574–583Google Scholar
  162. Spatz M, Mrsulja BB (1990): Monoamines and cerebral ischemia. In: Cerebral Ischemia and Resuscitation, Schurr A, Rigor, BM, eds. Boca Raton, Florida: CRC PressGoogle Scholar
  163. Suzuki R, Yamaguchi T, Choh-Luh L, Klatzo I (1983): The effects of 5-minute ischemia in Mongolian gerbils. II. Changes of spontaneous neuronal activity in cerebral cortex and CA1 sector of hippocampus. Acta Neuropathol (Berl) 60: 217–222Google Scholar
  164. Tagashira Y, Matsuda M, Welch KMA, Chabi E, Myer JS (1977): Effects of cyclic AMP and dibutyryl cyclic AMP on cerebral hemodynamics and metabolism in the baboon. J Neurosurg 46: 484–493PubMedGoogle Scholar
  165. Tomida S, Nowak TS Jr, Vass K, Lohr JM, Klatzo I (1987): Experimental model for repetitive ischemic attacks in gerbil: The cumulative effect of repeated ischemic insults. J Cereb Blood Flow Metab 7: 773–782PubMedGoogle Scholar
  166. Torregosa G, Terrasa JC, Salom JB, Miranda FJ, Campos V, Alborch E (1988): P1-purinoreceptors in the cerebral bed of goat in vivo. Eur J Pharmacol 149: 17–24Google Scholar
  167. Trost T, Stock K (1977): Effects of adenosine derivatives on cAMP accumulation and lipolysis in rat adipocytes and on adenylate cyclase in adipocyte plasma membranes. Naunyn-Schmiedbergs Arch Pharmacol 19: 33–40Google Scholar
  168. Trussel LO, Jackson MB (1987): Dependence of an adenosine-activated potassium current on a GTP-binding protein in mammalian central neurons. J Neurosci 10: 3306–3316Google Scholar
  169. van Calker D, Muller M, Hamprecht B (1979): Adenosine regulates two different types of receptors: The accumulation of cyclic AMP in cultured brain cells. J Neurochem 33: 999–1005PubMedGoogle Scholar
  170. Voll CL, Auer RN (1988): The effect of postischemic blood glucose levels on ischemic brain damage in the rat. Ann Neurol 24: 638–646PubMedPubMedCentralGoogle Scholar
  171. von Hanwehr R, Smith M-L, Siesjö BK (1986): Extra-and intracellular pH during near-complete forebrain ischemia in the rat. J Neurochem 46: 331–339Google Scholar
  172. von Lubitz DKJE, Dambrosia JM, Kempski O (1986a): Postischemic application of cyclohexyl adenosine (CHA) improvement of survival and of preservation of selectively vulnerable areas in gerbil. Abstr, X Int. Congr Neuropathol, Stockholm 1986 p 108Google Scholar
  173. von Lubitz DKJE, Dambrosia JM, Kempski O (1986b): Postischemic applications of cyclohexyl adenosine (CHA) in gerbils: Morphometric study of hippocampal CAI region. Abstr, X Int. Congr Neuropathol, Stockholm 1986 p 118Google Scholar
  174. von Lubitz DKJE, Dambrosia JM, Kempski O, Redmond DJ (1988): Cyclohexyl adenosine protects against neuronal death following ischemia in the CAI region of gerbil hippocampus. Stroke 19: 1133–1139Google Scholar
  175. von Lubitz DKJE, Dambrosia JM, Redmond DJ (1989): Protective effect of cyclohexyl adenosine in treatment of cerebral ischemia in gerbils. Neuroscience 2: 451–462Google Scholar
  176. von Lubitz DKE, Marangos PJ (1990): Cerebral ischemia in gerbils: Postischemic administration of cyclohexyl adenosine and 8-sulphophenyl-theophylline. J Mol Neurosci 2: 53–59Google Scholar
  177. Wauquier A, Van Belle H, Van den Brock WAE, Janssen PAJ (1987): Sleep improvement in dogs after oral administration of mioflazine, a nucleoside transport inhibitor. Psychopharmacology 91: 424–439Google Scholar
  178. Welsh FA, Sims RE, Harris V (1990): Mild hypothermia prevents ischemic injury in gerbil hippocampus. J Cereb Blood Flow Metab 10: 557–563PubMedGoogle Scholar
  179. White BC, Wiegenstein JG, Wenegar CD (1984): Brain ischemic anoxia. JAMA 12: 1587–1590Google Scholar
  180. Whittingham TS (1990): Aspects of brain energy metabolism and cerebral ischemia. In: Cerebral Ischemia and Resuscitation, Schurr A, Rigor BM, eds. Boca Raton, Florida: CRC PressGoogle Scholar
  181. Wojcik WJ, Neff NH (1983): Differential location of Al adenosine and A2 receptors in striatum. Neurosci Lett 41: 55–60PubMedGoogle Scholar
  182. Yamamoto M, Shima T, Uozumi T, Sogabe T, Yamada K, Kawasaki T (1983): A possible role of lipid peroxidation in cellular damages caused by cerebral ischemia and the protective effect of a-tocopherol administration. Stroke 14: 977–982PubMedGoogle Scholar
  183. Yeung SH, Fossom LH, Gill DL, Cooper DMF (1985): Magnesium exerts a central role in the regulation of inhibitory adenosine receptors. Biochem J 229: 91–100PubMedPubMedCentralGoogle Scholar

Copyright information

© Birkhäuser Boston 1992

Authors and Affiliations

  • K. J. Dag
  • E. von Lubitz
  • Paul J. Marangos

There are no affiliations available

Personalised recommendations