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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine diphosphate (8 mg per minute for five minutes) was infused into the carotid artery of 63 rabbits. The effects were twofold: systemic hypotension and platelet aggregation in the cerebral circulation. As a consequence of the last effect, platelet emboli were produced which occluded cerebral arteries in a number and size sufficient to cause cerebral ischemia. Areas of focal ischemia were observed through a cranial window, and documented with antipyrine autoradiography. Platelet thrombi were almost entirely transient, being fragmented and removed within a very short time of cessation of ADP infusion. Consequently, no permanent tissue damage ensued. This experimental model approaches the spontaneous transient ischemia attacks (TIAs) in man, demonstrating that these can be caused by pure platelet emboli. A high cholesterol diet administered for two months prior to ADP infusion did not enhance the effect of the procedure or make the platelet aggregation and the following ischemia longer in duration or more severe.
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PMID:Animal model of TIA: an experimental study with intracarotid ADP infusion in rabbits. 119 26

Several lines of evidence suggest that adenosine may be an endogenous protective agent in cerebral ischaemia. Adenosine is normally present in the extracellular fluid in most tissues of the body, including the brain, and its level increases dramatically following hypoxia or ischaemia. The rate of adenosine production is enhanced when the energy demand is larger than the rate of energy supply. Adenosine acts on specific receptors that are present in most cells in the body and that produce cellular effects that tend to antagonize a number of pathological events thought to be instrumental for ischaemic nerve cell death. Karl Rudolphi and colleagues review evidence for the neuroprotective potential of adenosine and indicate some targets for drug development.
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PMID:Neuroprotective role of adenosine in cerebral ischaemia. 129 70

The excitotoxic hypothesis suggests that cerebral ischemic damage results in part from the accumulation of the excitatory and potentially toxic neurotransmitters glutamate and aspartate. Adenosine, which also increases during cerebral ischemia, is proposed to inhibit neurotransmitter release. The purpose of this study was to determine if adenosine receptor blockade exacerbates the accumulation of glutamate and aspartate during cerebral ischemia. Microdialysis probes, implanted bilaterally in the caudate nucleus of halothane-anesthetized rats, were used to (1) assess changes in interstitial fluid (ISF) glutamate, aspartate, adenosine, and adenosine metabolites; (2) measure local cerebral blood flow (H2 clearance); and (3) deliver 8-(p-sulfophenyl)theophylline (SPT), an adenosine receptor antagonist, locally to the brain. The probe on one side of the brain was perfused with artificial cerebrospinal fluid (CSF) containing 10(-3) M SPT, while the probe on the opposite side received only artificial CSF. Animals were exposed to 20 min of ischemia (carotid occlusion+arterial blood pressure = 50 mm Hg) followed by 60 min of reperfusion. Dialysate glutamate and aspartate increased during and after cerebral ischemia, but were increased to a greater extent in the presence of adenosine receptor blockade. Likewise, the increase in dialysate adenosine and adenosine metabolites was enhanced on the side of locally administered SPT. These data suggest that endogenous adenosine attenuates the accumulation of glutamate and aspartate during cerebral ischemia.
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PMID:Adenosine receptor blockade augments interstitial fluid levels of excitatory amino acids during cerebral ischemia. 135 4

Basic neuroscience research findings during the past five years have established a clear relationship between the excitatory amino acid (EAA) neurotransmitters (glutamic and aspartic acid) and various pathological states. A major mechanism of neural tissue degeneration following cerebral ischemia, and perhaps other neurodegenerative diseases, seems to involve overactivity of the EAA system in brain. This process is called delayed excitotoxicity and it has become a focal point for the design of new drugs that inhibit its course (EAA receptor blockers). Very recently it has been shown that it is possible to block delayed excitotoxicity using adenosine A1 receptor agonists which inhibit EAA release pre-synaptically. This approach is very effective in reducing post-stroke neurological damage in a number of animal models and has certain advantages when compared to the EAA receptor blocker strategy. Adenosine agonists not only inhibit excitotoxicity but they also block granulocyte activation and the capillary no-reflow phenomenon which results. An additional adenosinergic approach involves brain permeable adenosine uptake blockers which would serve to increase adenosine levels somewhat selectively at ischemic foci thereby inhibiting EAA release. The adenosinergic approach to stroke therapeutics may be a potentially effective strategy for new drug development in neurology, and may have general applicability to other neurodegenerative disease states where excitotoxicity is being implicated.
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PMID:Adenosinergic approaches to stroke therapeutics. 197 12

Adenosine diphosphate-induced platelet aggregation and associated thromboxane B2 release were studied in 52 patients with subarachnoid hemorrhage (SAH) in order to detect a possible association between altered platelet function and development of cerebral ischemic complications after SAH. Compared to the values on admission, the patients showed significantly increased platelet aggregability (p less than 0.05) and thromboxane release (p less than 0.001) 1 to 2 weeks after SAH. The highest values of thromboxane release were seen in patients who deteriorated due to delayed cerebral ischemia with a permanent neurological deficit. Thromboxane release was significantly higher (p less than 0.05) before the onset of severe delayed ischemia in six patients with preoperative ischemia compared to the patients without delayed ischemia. In five others, both ischemic deterioration and elevated thromboxane release occurred after operation. These patients had preoperative values similar to the values in those without ischemic symptoms. The observations suggest that increased platelet aggregability and thromboxane release are associated with delayed cerebral ischemia both before and after surgery.
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PMID:Platelet thromboxane release and delayed cerebral ischemia in patients with subarachnoid hemorrhage. 199 3

The levels of adenosine in rat cerebral cortical superfusates were studied in rats prior to, and after, the administration of saline or D-glucose (3 g/kg). Hypoxia-evoked increases in purine release were significantly attenuated after glucose administration. After glucose administration, the falls in arterial blood pressure, which normally accompany systemic hypoxia, were reduced. To ensure that this was not the reason for the decrease in adenosine release, blood was withdrawn from a second group of hyperglycemic rats so that the post-glucose hypoxia was equivalent to the original control. Adenosine release was still significantly attenuated. This decrease in the levels of adenosine, a cerebroprotective agent, in the cerebral cortical extracellular space, may be a contributing factor to the detrimental effects of hyperglycemia on recovery from cerebral ischemia.
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PMID:The effect of hyperglycemia on extracellular levels of adenosine in the hypoxic rat cerebral cortex. 229 16

The present study investigated the effect of the administration of oxypurinol (40 mg/kg), an inhibitor of xanthine oxidase, on adenosine and adenine nucleotide levels in the rat brain during ischemia and reperfusion. The brains of the animals were microwaved before, at the end of a 20-min period of cerebral ischemia, and after 5, 10, 45, and 90 min of reperfusion. Cerebral ischemia was elicited by four-vessel occlusion with arterial hypotension to 45-50 mm Hg. Adenosine and adenine nucleotide levels in the oxypurinol-pretreated (administered intravenously 20 min before ischemia) rats were compared with those in nontreated animals exposed to the same periods of ischemia and reperfusion. Oxypurinol administration resulted in significantly elevated ATP levels at the end of ischemia and 5 min after ischemia, but not at 10 min after ischemia. ADP levels were also elevated, in comparison with those in the control rats, at the end of the ischemic period. Conversely, AMP levels were significantly reduced at the end of ischemia and during the initial (5 min) period of reperfusion. Adenosine levels were lower in oxypurinol-treated rats, during ischemia, and in the initial reperfusion phase. Oxypurinol administration resulted in a significant increase in the energy charge both during ischemia and after 5 min of reperfusion. Physiological indices, namely, time to recovery of mean arterial blood pressure and time to onset of respiration, were also shortened in the oxypurinol-treated animals. These beneficial effects of oxypurinol may have been a result of its purine-sparing (salvage) effects and of its ability to inhibit free radical formation by the enzyme xanthine oxidase. Preservation of high-energy phosphates during ischemia likely contributes to the cerebroprotective potency of oxypurinol.
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PMID:Oxypurinol-enhanced postischemic recovery of the rat brain involves preservation of adenine nucleotides. 772 3

The effects of indomethacin (10 mg/kg) on the release of the transmitter amino acids, glutamate, aspartate, GABA, and of the purines, adenosine and inosine, from the cerebral cortex was studied in a four-vessel occlusion rat model of cerebral ischemia/reperfusion. In comparison with the control group, indomethacin significantly attenuated the ischemia-evoked release of glutamate and aspartate, but not of GABA. Adenosine levels in the cortical superfusates were significantly elevated following indomethacin administration. As indomethacin is a potent inhibitor of adenosine uptake, these results suggest that, by blocking adenosine uptake, indomethacin could elevate extracellular adenosine levels and depress glutamate and aspartate efflux as a consequence of the activation of adenosine A1 receptors.
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PMID:Indomethacin modulates ischemia-evoked release of glutamate and adenosine from the rat cerebral cortex. 795 50

We examined the effects of adenosine, a putative mediator of neuroprotection during cerebral ischemia, on the electrophysiological characteristics of retina-retinal pigment epithelium-choroid preparations obtained from 1-7 day-old chick and maintained in vitro. Our experiments produced the following results. First, superfusion of the retinal surface with adenosine (0.1 mM) increased the trans-tissue potential. The trans-epithelial (but not the trans-retinal) potential was also increased to the same magnitude with a time-course similar to that of the trans-tissue potential. Second, adenosine produced a depolarization of the epithelial basal plasma membrane with a concomitant decrease in its basal membrane resistance. Third, the trans-epithelial (but not the trans-retinal) c-wave in response to a light stimulus was augmented by adenosine. Adenosine reduced the hyperpolarization of the epithelial basal membrane, but had no effect on the extracellular concentration of K+ in the subretinal region. Fourth, the light-peak that was elicited with a 300 s light stimulus was also depressed by adenosine. Fifth, when 4,4'-diisothiocy anostilbene-2,2'-disulfonate (DIDS), a relatively selective inhibitor of Cl- channels, was perfused at 50 microM on the choroidal surface, adenosine-induced increases in the trans-tissue potential and the c-wave were both abolished. These results suggest that adenosine increased the Cl- conductance of the basal plasma membrane of the retinal pigment epithelium and thereby augmented the standing potential as well as the light-elicited membrane potentials of the retinal pigment epithelium, which seems to be involved in the pathophysiology of retinal ischemia.
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PMID:Effects of adenosine on chick retinal pigment epithelium: membrane potentials and light-evoked responses. 852 4

Preliminary evidence suggests adenosine, a neuromodulator, has neuroprotective properties during cerebral ischemia. It is unclear, however, if adenosine has glioprotective effects. We studied the effect of adenosine on cellular injury in astroglial cultures subjected to combined glucose-oxygen deprivation. Adenosine (100-1,000 microM)dramatically reduced astroglial injury, whereas the adenosine agonists 2-chloroadenosine (10 nM-100 microM), N6-cyclopentyladenosine (1 nM-10 microM), 5'-N-ethylcarboxamidoadenosine (10 nM-100 microM), and N6-2-(4-aminophenyl)ethyladenosine (10 nM-100 microM) had no effect. Furthermore, the adenosine antagonists 8-cyclopentyl-1,3-dipropylxanthine (1 nM-1 microM), xanthine amine congener (10 nM-10 microM), and 8-(p-sulfophenyl)-theophylline (10-300 microM) failed to reverse the protective effect of 200 microM adenosine. Next, adenosine degradation products were studied. Inosine proved to be glioprotective at concentrations nearly identical to those of adenosine, but hypoxanthine and ribose had no effect. The protective effect of 200 microM inosine was not reversed by 8-(p-sulfophenyl)theophylline (10-300 microM). Adenosine deaminase (1 unit/ml) had no effect on protection produced by adenosine, whereas erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride (10 microM) reversed the protective effect of adenosine. Dipyridamole (4 microM) inhibited the protective effect of both adenosine and inosine. We conclude that adenosine dramatically decreases astroglial injury during combined glucose-oxygen deprivation and that this protective effect appears to be mediated by inosine.
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PMID:Inosine mediates the protective effect of adenosine in rat astrocyte cultures subjected to combined glucose-oxygen deprivation. 886 13


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