Protective Effect of Vinpocetine against Brain Damage Caused by Ischemia.

Rischke, Ralf; Krieglstein, Josef

doi:10.1254/jjp.56.349

Cited by 29 publications

(12 citation statements)

References 22 publications

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“…In vivo studies have shown that inhibition of the adenosine transporter increases extracellular adenosine 45 and attenuates ischemic damage. 6 ' 8 These results are consistent with the possibility that adenosine is formed extracellularly (by the breakdown of ATP and other adenine nucleotides released during the ischemic period), and the adenosine transporter serves to remove extracellular adenosine.…”

Section: Dipyridamole Increases Oxygen-glucosesupporting

confidence: 77%

Dipyridamole increases oxygen-glucose deprivation-induced injury in cortical cell culture.

Lobner

Choi

1994

Stroke

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Background and Purpose Adenosine transport inhibitors attenuate ischemic central neuronal damage in vivo, but the locus of this protective action is presently unknown. To help address the question of whether adenosine transport inhibitors have a protective effect directly on brain parenchyma, we tested the effect of the adenosine transport inhibitor dipyridamole on neuronal loss induced by oxygen-glucose deprivation in vitro.Methods Murine cortical cultures were exposed to combined oxygen and glucose deprivation, iV-methyl-D-aspartate, or kainate. The extracellular concentrations of glutamate and adenosine were measured by high-performance liquid chromatography; neuronal cell death was assessed by morphological examination and measurement of lactate dehydrogenase release.Results Cultures exposed to oxygen-glucose deprivation for 30 to 75 minutes exhibited an insult-dependent increase in extracellular adenosine, followed shortly by an increase in E xtracellular adenosine levels have been shown to increase during reduced energy conditions both in vivo 1 -2 and in vitro. 3 However, the source of the extracellular adenosine is not known. In vivo studies have shown that inhibition of the adenosine transporter increases extracellular adenosine 45 and attenuates ischemic damage.6 ' 8 These results are consistent with the possibility that adenosine is formed extracellularly (by the breakdown of ATP and other adenine nucleotides released during the ischemic period), and the adenosine transporter serves to remove extracellular adenosine.However, adenosine transport inhibitors are known to have multiple effects. Specifically, dipyridamole has been shown to potentiate hypoxic pial arteriolar vasodilation 9 and increase cerebral blood flow during anoxia.10 Thus, the protective effects of adenosine transport inhibitors could be primarily due to effects on blood flow. Furthermore, in vitro studies using neurons 11 Addition of the Al receptor antagonist 8-cyclopentyltheophylline during oxygen-glucose deprivation enhanced both glutamate release and neuronal damage. Addition of 10 ^.mol/L dipyridamole decreased extracellular adenosine and also enhanced extracellular glutamate and neuronal death. In contrast, dipyridamole increased the levels of extracellular adenosine stimulated by Af-methyl-D-aspartate or kainate.Conclusions These results are consistent with the idea that endogenous adenosine has a neuroprotective effect directly on cortical cells exposed to oxygen-glucose deprivation. However, inhibition of adenosine transport with dipyridamole was surprisingly not an effective strategy for enhancing this protective effect. The beneficial effects of adenosine transport inhibitors observed in vivo may be mediated indirectly-for example, by effects on the vasculature. To help address the question of whether adenosine transport inhibitors have a protective effect directly on brain parenchyma, we tested the effect of dipyridamole on the neuronal loss induced by oxygen-glucose deprivation in murine cortical cell cultures. Material...

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Section: Dipyridamole Increases Oxygen-glucosesupporting

confidence: 77%

Dipyridamole increases oxygen-glucose deprivation-induced injury in cortical cell culture.

Lobner

Choi

1994

Stroke

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“…Beneficial effects on neurological symptoms have been claimed in several clinical studies [62], Recently ( fig. 5g), it has been shown that vinpocetine reduces hippocampal neuronal damage caused by transient forebrain ischemia [63] as well as after middle cerebral artery occlusion [64]. Vinpocetine clearly prevented the changes in hippocampal CMRglcand CBF values 7 days after ischemia [65].…”

Section: A Denosine Agonistsmentioning

confidence: 94%

Brain Damage Caused by Ischemia: Pathophysiological and Pharmacological Aspects

Rami

Krieglstein²

1993

Dement Geriatr Cogn Disord

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The distribution of brain cell injury after ischemic challenge is remarkable because only discrete brain areas are damaged, whereas other structures exhibit a very high resistance (selective neuronal death). The calcium hypothesis, one of the hypotheses that has been formulated to explain this selective vulnerability, postulates that an increase in excitatory amino acid release and the large calcium influx during ischemia leads to insufficient energy production and to stimulation of lipases, proteases, and endonucleases. This paper reviews the experimental data concerning the relationship between cerebral blood flow, glucose consumption and hippocampal morphological damage. The neuroprotective effects of some drugs against ischemic damage have also been discussed.

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“…Using animal models of ischemia, investigators have found neuroprotective effects from vinpocetine. Rischke and Krieglstein (1991) examined hippocampal damage in rats 7 days after experimentally induced cerebral ischemia. Among control rats, 77% of hippocampal neurons were damaged, whereas in rats given 10 mg/kg of vinpocetine (either before or after the ischemia), damage was reduced to 37% of the hippocampal neurons.…”

Section: Mechanisms and Animal Studiesmentioning

confidence: 99%

“Brain-Specific” Nutrients: A Memory Cure?

McDaniel

Maier

Einstein

2002

Psychol Sci Public Interest

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We review the experimental evaluations of several widely marketed nonprescription compounds claimed to be memory enhancers and treatments for age-related memory decline. We generally limit our review to double-blind placebo-controlled studies. The compounds examined are phos-phatidylserine (PS), phosphatidylcholine (PC), citicoline, piracetam, vinpocetine, acetyl-L-carnitine (ALC), and antiox-idants (particularly vitamin E). In animals, PS has been shown to attenuate many neuronal effects of aging, and to restore normal memory on a variety of tasks. Preliminary findings with humans, though, are limited. For older adults with probable Alzheimer's disease, a single study failed to demonstrate positive effects of PS on memory performance. For older adults with moderate cognitive impairment, PS has produced consistently modest increases in recall of word lists. Positive effects have not been as consistently reported for other memory tests. There is one report of consistent benefits across a number of memory tests for a subset of normal adults who performed more poorly than their peers at baseline. The choline compounds PC and citicoline are thought to promote synthesis and transmission of neurotransmitters important to memory. PC has not proven effective for improving memory in patients with probable Alzheimer's disease. The issue remains open for older adults without serious degenerative neural disease. Research on citicoline is practically nonexistent, but one study reported a robust improvement in story recall for a small sample of normally aging older adults who scored lower than their peers in baseline testing. Animal studies suggest that piracetam may improve neuronal efficiency, facilitate activity in neurotransmitter systems, and combat the age-related decrease in receptors on the neuronal membrane. However, for patients with probable Alzheimer's disease, as well as for adults with age-associated memory impairment, there is no clear-cut support for a mnemonic benefit of piracetam. Vinpocetine increases blood circulation and metabolism in the brain. Animal studies have shown that vinpocetine can reduce the loss of neurons due to decreased blood flow. In three studies of older adults with memory problems associated with poor brain circulation or dementia-related disease, vinpocetine produced significantly more improvement than a placebo in performance on global cognitive tests reflecting attention, concentration, and memory. Effects on episodic memory per se have been tested minimally, if at all. ALC participates in cellular energy production, a process especially important in neurons, and in removal of toxic accumulation of fatty acids. Animal studies show that ALC reverses the age-related decline in the number of neuron membrane receptors. Studies of patients with probable Alzheimer's disease have reported nominal advantages over a range of memory tests for ALC-treated patients relative to placebo groups. Significant differences have been reported rarely, however. Whether ALC would have mnemonic benefits for ...

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Protective Effect of Vinpocetine against Brain Damage Caused by Ischemia.

Cited by 29 publications

References 22 publications

Dipyridamole increases oxygen-glucose deprivation-induced injury in cortical cell culture.

Dipyridamole increases oxygen-glucose deprivation-induced injury in cortical cell culture.

Brain Damage Caused by Ischemia: Pathophysiological and Pharmacological Aspects

“Brain-Specific” Nutrients: A Memory Cure?

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