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. 1996 Jul;118(6):1551–1557. doi: 10.1111/j.1476-5381.1996.tb15573.x

Block by N6-L-phenylisopropyl-adenosine of the electrophysiological and morphological correlates of hippocampal ischaemic injury in the gerbil.

M R Domenici 1, A S de Carolis 1, S Sagratella 1
PMCID: PMC1909677  PMID: 8832085

Abstract

1. The effects of the mixed A1 and A2 adenosine receptor agonist N6-L-phenyl-isopropyladenosine (L-PIA) were tested on ischaemia-induced hippocampal neuronal injury in gerbils subjected to 5-min bilateral carotid occlusion. For comparison, the effects of the selective A2 adenosine receptor agonist, CGS 21680 were tested. 2. Five-min bilateral carotid occlusion produced within 1 week an irreversible suppression of the CA1, but not of the dentate extracellular electrical somatic responses, in 30% of gerbil hippocampal slices with respect to controls. In addition, a significant reduction occurred in the density of CA1 hippocampal pyramidal neurones but not of dentate granule cells with respect to controls. 3. Injection 1 h before or after bilateral carotid occlusion of L-PIA (0.8-1.5 mg kg-1, i.p.) but not of CGS 21680 (5 mg kg-1, i.p.), significantly prevented the irreversible disappearance of the CA1 extracellular electrical somatic responses with respect to controls. In addition, the CA1 pyramidal neuronal loss was also prevented. 4. The results show that activation of A1 adenosine receptors is able to prevent or block the electrophysiological and morphological correlates of hippocampal neuronal injury after global ischaemia in the gerbil, suggesting that adenosine receptor agonists might have a useful role in the treatment of neuronal functional and anatomical injury due to ischaemia.

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Selected References

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  1. Boissard C. G., Gribkoff V. K. The effects of the adenosine reuptake inhibitor soluflazine on synaptic potentials and population hypoxic depolarizations in area CA1 of rat hippocampus in vitro. Neuropharmacology. 1993 Feb;32(2):149–155. doi: 10.1016/0028-3908(93)90095-k. [DOI] [PubMed] [Google Scholar]
  2. Burke S. P., Nadler J. V. Regulation of glutamate and aspartate release from slices of the hippocampal CA1 area: effects of adenosine and baclofen. J Neurochem. 1988 Nov;51(5):1541–1551. doi: 10.1111/j.1471-4159.1988.tb01123.x. [DOI] [PubMed] [Google Scholar]
  3. Chang H. S., Sasaki T., Kassell N. F. Hippocampal unit activity after transient cerebral ischemia in rats. Stroke. 1989 Aug;20(8):1051–1058. doi: 10.1161/01.str.20.8.1051. [DOI] [PubMed] [Google Scholar]
  4. Choi D. W. Ionic dependence of glutamate neurotoxicity. J Neurosci. 1987 Feb;7(2):369–379. doi: 10.1523/JNEUROSCI.07-02-00369.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Corradetti R., Lo Conte G., Moroni F., Passani M. B., Pepeu G. Adenosine decreases aspartate and glutamate release from rat hippocampal slices. Eur J Pharmacol. 1984 Sep 3;104(1-2):19–26. doi: 10.1016/0014-2999(84)90364-9. [DOI] [PubMed] [Google Scholar]
  6. Dolphin A. C., Archer E. R. An adenosine agonist inhibits and a cyclic AMP analogue enhances the release of glutamate but not GABA from slices of rat dentate gyrus. Neurosci Lett. 1983 Dec 23;43(1):49–54. doi: 10.1016/0304-3940(83)90127-1. [DOI] [PubMed] [Google Scholar]
  7. Dolphin A. C. The adenosine agonist 2-chloroadenosine inhibits the induction of long-term potentiation of the perforant path. Neurosci Lett. 1983 Aug 19;39(1):83–89. doi: 10.1016/0304-3940(83)90169-6. [DOI] [PubMed] [Google Scholar]
  8. Domenici M. R., Longo R., de Carolis A. S., Frank C., Sagratella S. Protective actions of 21-aminosteroids and MK-801 on hypoxia-induced electrophysiological changes in rat hippocampal slices. Eur J Pharmacol. 1993 Mar 23;233(2-3):291–293. doi: 10.1016/0014-2999(93)90064-o. [DOI] [PubMed] [Google Scholar]
  9. Dragunow M., Faull R. L. Neuroprotective effects of adenosine. Trends Pharmacol Sci. 1988 Jun;9(6):193–194. doi: 10.1016/0165-6147(88)90079-x. [DOI] [PubMed] [Google Scholar]
  10. Dunwiddie T. V. Endogenously released adenosine regulates excitability in the in vitro hippocampus. Epilepsia. 1980 Oct;21(5):541–548. doi: 10.1111/j.1528-1157.1980.tb04305.x. [DOI] [PubMed] [Google Scholar]
  11. Evans M. C., Swan J. H., Meldrum B. S. An adenosine analogue, 2-chloroadenosine, protects against long term development of ischaemic cell loss in the rat hippocampus. Neurosci Lett. 1987 Dec 29;83(3):287–292. doi: 10.1016/0304-3940(87)90101-7. [DOI] [PubMed] [Google Scholar]
  12. Fastbom J., Fredholm B. B. Inhibition of [3H] glutamate release from rat hippocampal slices by L-phenylisopropyladenosine. Acta Physiol Scand. 1985 Sep;125(1):121–123. doi: 10.1111/j.1748-1716.1985.tb07698.x. [DOI] [PubMed] [Google Scholar]
  13. Fowler J. C. Adenosine antagonists delay hypoxia-induced depression of neuronal activity in hippocampal brain slice. Brain Res. 1989 Jun 26;490(2):378–384. doi: 10.1016/0006-8993(89)90258-8. [DOI] [PubMed] [Google Scholar]
  14. Frank C., Sagratella S., Benedetti M., Scotti de Carolis A. Comparative influence of calcium blocker and purinergic drugs on epileptiform bursting in rat hippocampal slices. Brain Res. 1988 Feb 16;441(1-2):393–397. doi: 10.1016/0006-8993(88)91421-7. [DOI] [PubMed] [Google Scholar]
  15. Frank C., Scotti de Carolis A., Sagratella S. Influence of adenosinergic drugs on the epileptiform and neurotoxic effects of N-methyl-d-aspartate: comparison with the effects of MK801. Arch Int Pharmacodyn Ther. 1994 Jan-Feb;327(1):3–12. [PubMed] [Google Scholar]
  16. Goldberg M. P., Monyer H., Weiss J. H., Choi D. W. Adenosine reduces cortical neuronal injury induced by oxygen or glucose deprivation in vitro. Neurosci Lett. 1988 Jul 8;89(3):323–327. doi: 10.1016/0304-3940(88)90547-2. [DOI] [PubMed] [Google Scholar]
  17. Greene R. W., Haas H. L. The electrophysiology of adenosine in the mammalian central nervous system. Prog Neurobiol. 1991;36(4):329–341. doi: 10.1016/0301-0082(91)90005-l. [DOI] [PubMed] [Google Scholar]
  18. Hagberg H., Andersson P., Lacarewicz J., Jacobson I., Butcher S., Sandberg M. Extracellular adenosine, inosine, hypoxanthine, and xanthine in relation to tissue nucleotides and purines in rat striatum during transient ischemia. J Neurochem. 1987 Jul;49(1):227–231. doi: 10.1111/j.1471-4159.1987.tb03419.x. [DOI] [PubMed] [Google Scholar]
  19. Hartley D. M., Choi D. W. Delayed rescue of N-methyl-D-aspartate receptor-mediated neuronal injury in cortical culture. J Pharmacol Exp Ther. 1989 Aug;250(2):752–758. [PubMed] [Google Scholar]
  20. Jørgensen M. B., Diemer N. H. Selective neuron loss after cerebral ischemia in the rat: possible role of transmitter glutamate. Acta Neurol Scand. 1982 Nov;66(5):536–546. doi: 10.1111/j.1600-0404.1982.tb03140.x. [DOI] [PubMed] [Google Scholar]
  21. Kahn K. The natural course of experimental cerebral infarction in the gerbil. Neurology. 1972 May;22(5):510–515. doi: 10.1212/wnl.22.5.510. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Lee K. S., Schubert P., Heinemann U. The anticonvulsive action of adenosine: a postsynaptic, dendritic action by a possible endogenous anticonvulsant. Brain Res. 1984 Oct 29;321(1):160–164. doi: 10.1016/0006-8993(84)90694-2. [DOI] [PubMed] [Google Scholar]
  24. Lupica C. R., Cass W. A., Zahniser N. R., Dunwiddie T. V. Effects of the selective adenosine A2 receptor agonist CGS 21680 on in vitro electrophysiology, cAMP formation and dopamine release in rat hippocampus and striatum. J Pharmacol Exp Ther. 1990 Mar;252(3):1134–1141. [PubMed] [Google Scholar]
  25. MacGregor D. G., Miller W. J., Stone T. W. Mediation of the neuroprotective action of R-phenylisopropyl-adenosine through a centrally located adenosine A1 receptor. Br J Pharmacol. 1993 Sep;110(1):470–476. doi: 10.1111/j.1476-5381.1993.tb13834.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mager R., Ferroni S., Schubert P. Adenosine modulates a voltage-dependent chloride conductance in cultured hippocampal neurons. Brain Res. 1990 Nov 5;532(1-2):58–62. doi: 10.1016/0006-8993(90)91741-x. [DOI] [PubMed] [Google Scholar]
  27. McIlwain H., Poll J. D. Adenosine in cerebral homeostatic role: appraisal through actions of homocysteine, colchicine, and dipyridamole. J Neurobiol. 1986 Jan;17(1):39–49. doi: 10.1002/neu.480170105. [DOI] [PubMed] [Google Scholar]
  28. Meldrum B. Possible therapeutic applications of antagonists of excitatory amino acid neurotransmitters. Clin Sci (Lond) 1985 Feb;68(2):113–122. doi: 10.1042/cs0680113. [DOI] [PubMed] [Google Scholar]
  29. Murray T. F., Cheney D. L. Neuronal location of N6-cyclohexyl[3H]adenosine binding sites in rat and guinea-pig brain. Neuropharmacology. 1982 Jun;21(6):575–580. doi: 10.1016/0028-3908(82)90050-8. [DOI] [PubMed] [Google Scholar]
  30. Phillis J. W., Kostopoulos G. K., Limacher J. J. Depression of corticospinal cells by various purines and pyrimidines. Can J Physiol Pharmacol. 1974 Dec;52(6):1226–1229. doi: 10.1139/y74-162. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Rudolphi K. A., Schubert P., Parkinson F. E., Fredholm B. B. Adenosine and brain ischemia. Cerebrovasc Brain Metab Rev. 1992 Winter;4(4):346–369. [PubMed] [Google Scholar]
  33. Sheardown M. J., Suzdak P. D., Nordholm L. AMPA, but not NMDA, receptor antagonism is neuroprotective in gerbil global ischaemia, even when delayed 24 h. Eur J Pharmacol. 1993 Jun 4;236(3):347–353. doi: 10.1016/0014-2999(93)90470-3. [DOI] [PubMed] [Google Scholar]
  34. Sutherland G. R., Peeling J., Lesiuk H. J., Brownstone R. M., Rydzy M., Saunders J. K., Geiger J. D. The effects of caffeine on ischemic neuronal injury as determined by magnetic resonance imaging and histopathology. Neuroscience. 1991;42(1):171–182. doi: 10.1016/0306-4522(91)90157-j. [DOI] [PubMed] [Google Scholar]
  35. Urban L., Neill K. H., Crain B. J., Nadler J. V., Somjen G. G. Postischemic synaptic physiology in area CA1 of the gerbil hippocampus studied in vitro. J Neurosci. 1989 Nov;9(11):3966–3975. doi: 10.1523/JNEUROSCI.09-11-03966.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Valentino K., Newcomb R., Gadbois T., Singh T., Bowersox S., Bitner S., Justice A., Yamashiro D., Hoffman B. B., Ciaranello R. A selective N-type calcium channel antagonist protects against neuronal loss after global cerebral ischemia. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7894–7897. doi: 10.1073/pnas.90.16.7894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Von Lubitz D. K., Lin R. C., Melman N., Ji X. D., Carter M. F., Jacobson K. A. Chronic administration of selective adenosine A1 receptor agonist or antagonist in cerebral ischemia. Eur J Pharmacol. 1994 Apr 21;256(2):161–167. doi: 10.1016/0014-2999(94)90241-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Yassin M., Scholfield C. N. NMDA antagonists increase recovery of evoked potentials from slices of rat olfactory cortex after anoxia. Br J Pharmacol. 1994 Apr;111(4):1221–1227. doi: 10.1111/j.1476-5381.1994.tb14875.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Zeng Y. C., Domenici M. R., Frank C., Sagratella S., Scotti de Carolis A. Effects of adenosinergic drugs on hypoxia-induced electrophysiological changes in rat hippocampal slices. Life Sci. 1992;51(13):1073–1082. doi: 10.1016/0024-3205(92)90507-l. [DOI] [PubMed] [Google Scholar]
  40. van Calker D., Müller M., Hamprecht B. Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. J Neurochem. 1979 Nov;33(5):999–1005. doi: 10.1111/j.1471-4159.1979.tb05236.x. [DOI] [PubMed] [Google Scholar]

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