Progress in Understanding the Pathophysiology of Cerebral Ischemia: The Almitrine-Raubasine Approach

Bentué-Ferrer, Danièle; Decombe, R.; Reymann, Jeane-Michel; Schatz, Christian; Allain, H.

doi:10.1097/00002826-199013003-00002

Cited by 11 publications

(4 citation statements)

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“…Speculatively, therefore, preischemic injection of IB-MECA may initiate structural and functional changes in microvascular and neuronal membranes prior to the insult. In turn, such 'priming' of both neurons and microvessels may increase their sensitivity to a repeated sequence of the same injurious events (Siesjö, 1981) elicited by the subsequent arrest of cerebral circulation (Bazan, 1989;Bantue-Ferrer et al, 1990;Bazan and Cluzel, 1992;Mattson et al, 1993). Moreover, severe postocclusive perturbations of MABP and cerebral blood flow that accompany acute administration of IB-MECA may enhance the mismatch between metabolic demand and supply of postischemically hyperactivated brain (Suzuki et al, 1983;Ginsberg et al, 1985;Hossman et al, 1976) enhancing the damage even further.…”

Section: Discussionmentioning

confidence: 99%

Adenosine A3 receptor stimulation and cerebral ischemia

Lubitz

Lin

Popik

et al. 1994

European Journal of Pharmacology

271

257

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Chronic treatment with the selective adenosine A 3 receptor agonist N 6 -(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 A 1 nor A 2 receptors are involved in these actions. The data indicate that stimulation of adenosine A 3 receptors may play an important role in the development of ischemic damage, and that adenosine A 3 receptors may offer a new target for therapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

Adenosine A3 receptor stimulation and cerebral ischemia

Lubitz

Lin

Popik

et al. 1994

European Journal of Pharmacology

271

257

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“…There is a body of evidence that an excess of free radicals derived from oxygen are formed during ischaemia\reperfusion of various tissues, which causes the impairment of cellular components [1][2][3][4][5][6]. Furthermore, the ability of isolated hepatocytes to produce large quantities of oxygen free radicals during post-anoxic reoxygenation has recently been demonstrated [7,8].…”

Section: Introductionmentioning

confidence: 99%

Short-term impairment of energy production in isolated rat liver mitochondria by hypoxia/reoxygenation: involvement of oxidative protein modification

Schild

Reinheckel

Wiswedel

et al. 1997

Biochemical Journal

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The aim of the present study was to elucidate the role of mitochondria in liver impairment after ischaemia/reperfusion. It is commonly assumed that mitochondria are in part responsible for tissue damage by impaired oxidative phosphorylation as a consequence of the attack of radicals generated within the mitochondria. The principal support for this hypothesis was found by exposing isolated mitochondria to temporary hypoxia in combination with alterations of substrate supply. Rat liver mitochondria treated in this way responded with impaired ADP-stimulated respiration after reoxygenation, which decreased with time of hypoxia and reoxygenation. The decline of the activity of the NADH-cytochrome c-oxidoreductase complex found under these conditions is likely to cause the drop in active respiration. No changes in the content of respiratory chain complexes, determined by Blue Native PAGE, could be demonstrated. However, oxidative modifications of mitochondrial proteins, indicated by carbonyl formation, were found. Likewise, products of lipid peroxidation, such as lipid peroxides and malondialdehyde, were formed. Mitochondria were still able to build up a transmembrane potential and did not show drastic changes in membrane conductivity after hypoxia/reoxygenation stress. The presence of water-soluble antioxidants exhibited a beneficial effect, diminishing the decline of active respiration after 5 min of hypoxia and 10 min of reoxygenation. These observations strongly suggest that mitochondria play a pathogenic role in ischaemia/reperfusion injury, which is at least in part mediated by an oxygen-derived free-radical-linked mechanism.

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“…In a model of unilateral carotid ligature in the gerbil, GM1 (or AG 12) reduced by 52% the mortality at 48 h and reduced the size of the infarction [68], These results have been controlled in man. The role of scavengers trapping free radicals remains controversial [62,[69][70][71], New molecules have appeared in the literature, such as MCI 186 [72], Finally, the protective role of RX 77368. a thyrotropin-releasing hormone analog, through possible vascular action is mentioned [73]. The hcmorrheological or fibrinolytic targets have deliberately been left out of this review, although these vascular avenues of investigation merit great consideration.…”

Section: Other Pharmacologic Approachesmentioning

confidence: 99%

Mechanistic Basis for the Development of Anti-Ischemic Drugs

Allain¹,

Decombe²,

Saiag³

et al. 1991

Cerebrovasc Dis

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The pharmacology of cerebral ischemia features 100 molecules and 20 potentially interesting mechanisms for preventing the tissue damage induced by anoxia-ischemia. The intricacy and complexity of the mechanisms involved probably account for the absence of definite evidence for effectiveness in man. The molecules which act on mechanisms qualifying as common denominators or triggering off cascade reactions, appear to be the best candidates. In this respect, the action of calcium, neurotransmitters, excitatory amino acids and pyrimidinergic or purinergic processes has to be given priority. Guidelines for the development of anti-ischemic molecules should be issued urgently, insisting on models, evaluation criteria, intervention timing and the parameters to be monitored (e.g. temperature, glycemia, choice of animal species).

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Progress in Understanding the Pathophysiology of Cerebral Ischemia: The Almitrine-Raubasine Approach

Cited by 11 publications

References 0 publications

Adenosine A3 receptor stimulation and cerebral ischemia

Adenosine A3 receptor stimulation and cerebral ischemia

Short-term impairment of energy production in isolated rat liver mitochondria by hypoxia/reoxygenation: involvement of oxidative protein modification

Mechanistic Basis for the Development of Anti-Ischemic Drugs

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