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. 1994 Sep 22;263(1-2):59-67.
doi: 10.1016/0014-2999(94)90523-1.

Adenosine A3 receptor stimulation and cerebral ischemia

D K Von Lubitz  1 , R C Lin, P Popik, M F Carter, K A Jacobson
Affiliations

Adenosine A3 receptor stimulation and cerebral ischemia

D K Von Lubitz et al. Eur J Pharmacol. .

Abstract

Chronic treatment with the selective adenosine A3 receptor agonist N6-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (IB-MECA) administered prior to either 10 or 20 min forebrain ischemia in gerbils resulted in improved postischemic cerebral blood circulation, survival, and neuronal preservation. Opposite effects, i.e., impaired postischemic blood flow, enhanced mortality, and extensive neuronal destruction in the hippocampus were seen when IB-MECA was given acutely. Neither adenosine A1 nor A2 receptors are involved in these actions. The data indicate that stimulation of adenosine A3 receptors may play an important role in the development of ischemic damage, and that adenosine A3 receptors may offer a new target for therapeutic interventions.

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Figures

Fig. 1
Fig. 1
Pre-, intra-, and postischemic (10 min ischemia) temperature of controls (open circles), animals injected either acutely (black triangles) or chronically (black circles) with IB-MECA (n = 15/group). Pre: epicranial temperature 10 min prior to ischemia; 0: epicranial temperature at 30 s prior to the release of the occlusion. After 10 min postischemia, only rectal temperatures are given (n = 15/group).
Fig. 2
Fig. 2
Blood flow rate (CBFR) changes during and after 10 min ischemia. Open circles: controls; black triangles: acute IB-MECA; black circles: chronic IB-MECA (n = 5/group).
Fig. 3
Fig. 3
Survival rate following 10 min ischemia. Controls: open circles; acute IB-MECA: black triangles; chronic IB-MECA: black circles (n = 15/group).
Fig. 4
Fig. 4
Neuronal preservation in the CA1 sector of the hippocampus following 10 min ischemia. Since only one animal survived in the acutely injected group, no range bar is given.
Fig. 5
Fig. 5
(A) A segment of the CA1 sector in the solitary survivor of the acute treatment with IB-MECA prior to 10 min ischemia. Note virtually complete destruction of the pyramidal cells. Arrows in (A), (B), and (C): neurons with intact morphology. (B) Control gerbil 7 days after 10 min ischemia. The photograph shows CA1 from the same area as that shown in (A). There is a limited preservation of neurons. (C) Extensive neuroprotection of the CA1 after chronic treatment with IB-MECA prior to 10 min ischemia. Same area as in (A) and (B). Scale bar for (A), (B), and (C): 100 µm.
Fig. 6
Fig. 6
End-point survival of controls and animals given chronic treatment with IB-MECA prior to 20 min ischemia. No acutely treated gerbils survived to the end point (see text for details).
Fig. 7
Fig. 7
Neuronal preservation in controls and animals treated chronically with IB-MECA prior to 20 min ischemia.
See this image and copyright information in PMC

References

    1. Abbracchio MP, Fogliatto G, Paoletti AM, Rovati GE, Cattabeni F. Prolonged in vitro exposure of rat brain slices to adenosine analogues: selective desensitization of adenosine A1 but not A2 receptors. Eur. J. Pharmacol. Mol. Pharmacol. 1992;227:317. - PubMed
    1. Ali H, Cunha-Melo JR, Saul WF, Beaven MA. Activation of phospholipase C via adenosine receptors provides synergistic signals for secretion in antigen stimulated RBL-2H3 cells. Evidence for a novel adenosine receptor. J. Biol. Chem. 1990;15:745. - PubMed
    1. Ames A, Wright RL, Kowada M, Thurston JM, Majno G. Cerebral ischemia. II. The no-reflow phenomenon. Am. J. Pathol. 1968;52:437. - PMC - PubMed
    1. Aspey BS, Ehtesami S, Hurst CM, McCoy AL, Harrison MJG. The effect of increased blood pressure on hemispheric lactate and water content during acute cerebral ischemia in the rat and gerbil. J. Neurol. Neurosurg. Psychiatry. 1987;50:1493. - PMC - PubMed
    1. Bantue-Ferrer B, Decombe R, Reymann JM, Schgatz C, Allain H. Progress in understanding the pathophysiology of cerebral isehemia: the almitrine-raubasine approach. Clin. Neuropharmacol. 1990;13(Suppl. 3):S9. - PubMed

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