Neuroprotection and glutamate attenuation by acetylsalicylic acid in temporary but not in permanent cerebral ischemia

Berger, Christian; Stauder, A.; Feng, Xia; Sommer, Clemens; Schwab, Stefan

doi:10.1016/j.expneurol.2007.12.002

Cited by 38 publications

(23 citation statements)

References 27 publications

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“…18 NMDA antagonists have a narrow therapeutic window, 46 consistent with normalization of extracellular glutamate concentrations shortly after restoration of circulation from MCAO. 47 Our data showed a beneficial effect of xenon begun after transient MCAO that was reproducible and independent of temperature in a 7-day recovery model. We then conducted a longer-term (28 days) MCAO outcome efficacy analysis.…”

Section: Discussionsupporting

confidence: 56%

Xenon Neuroprotection in Experimental Stroke

Sheng

Lei²,

James³

et al. 2012

Anesthesiology

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Background: Xenon has been proven to be neuroprotective in experimental brain injury. The authors hypothesized that xenon would improve outcome from focal cerebral ischemia with a delayed treatment onset and prolonged recovery interval. Methods: Rats were subjected to 70 min temporary focal ischemia. Ninety minutes later, rats were treated with 0, 15, 30, or 45% Xe for 20 h or 0 or 30% Xe for 8, 20, or 44 h. Outcome was measured after 7 days. In another experiment, after ischemia, rats were maintained at 37.5° or 36.0°C for 20 h with or without 30% Xe. Outcome was assessed 28 days later. Finally, mice were subjected to intracerebral hemorrhage with or without 30% Xe for 20 h. Brain water content, hematoma volume, rotarod function, and microglial activation were measured.Results: Cerebral infarct sizes (mean ± SD) for 0, 15, 30, and 45% Xe were 212 ± 27, 176 ± 55, 160 ± 32, and 198 ± 54 mm 3 , respectively (P = 0.023). Neurologic scores (median ± interquartile range) followed a similar pattern (P = 0.002). Infarct size did not vary with treatment duration, but neurologic score improved (P = 0.002) at all xenon exposure durations (8, 20, and 44 h). Postischemic treatment with either 30% Xe or subtherapeutic hypothermia (36°C) had no effect on 28-day outcome. Combination of these interventions provided long-term benefit. Xenon improved intracerebral hemorrhage outcome measures. Conclusion: Xenon improved focal ischemic outcome at 7, but not 28 days postischemia. Xenon combined with subtherapeutic hypothermia produced sustained recovery benefit. Xenon improved intracerebral hemorrhage outcome. Xenon may have potential for clinical stroke therapy under carefully defined conditions.

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Section: Discussionsupporting

confidence: 56%

Xenon Neuroprotection in Experimental Stroke

Sheng

Lei²,

James³

et al. 2012

Anesthesiology

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“…Treatments with tempol are known to reduce production of arachidonic acid metabolites, such as prostocyclins and thromboxanes, in various preparations and in vivo , (reviewed in [84]). Since two previous studies demonstrated that the cyclooxygenase inhibitor aspirin alleviate the intraischemic glutamate release and brain damage in rat MCAo [85, 86], the link to arachidonic acid metabolism deserves further exploration. An additional mechanism that may contribute to glutamate release and involve O 2 •− is the formation of ONOO − , which has been found to stimulate glial VRAC in vitro [32].…”

Section: Discussionmentioning

confidence: 99%

The neuroprotective properties of the superoxide dismutase mimetic tempol correlate with its ability to reduce pathological glutamate release in a rodent model of stroke

Dohare

Hyzinski‐García

Vipani

et al. 2014

Free Radical Biology and Medicine

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The contribution of oxidative stress to ischemic brain damage is well established. Nevertheless, for unknown reasons, several clinically tested antioxidant therapies failed to show benefits in human stroke. Based on our previous in vitro work, we hypothesized that the neuroprotective potency of antioxidants is related to their ability to limit release of the excitotoxic amino acids, glutamate and aspartate. We explored the effects of two antioxidants, tempol and edaravone, on amino acid release in the brain cortex, in a rat model of transient occlusion of the middle cerebral artery (MCAo). Amino acid levels were quantified using a microdialysis approach, with the probe positioned in the ischemic penumbra as verified by a laser Doppler technique. Two-hour MCAo triggered a dramatic increase in the levels of glutamate, aspartate, taurine and alanine. Microdialysate delivery of 10 mM tempol reduced the amino acid release by 60–80%, while matching levels of edaravone had no effect. In line with these latter data, an intracerebroventri-cular injection of tempol but not edaravone (500 nmols each, 15 minutes prior to MCAo) reduced infarction volumes by ~50% and improved neurobehavioral outcomes. In vitro assays showed that tempol was superior in removing superoxide anion, whereas edaravone was more potent in scavenging hydrogen peroxide, hydroxyl radical, and peroxynitrite. Overall, our data suggests that the neuroprotective properties of tempol are likely related to its ability to reduce tissue levels of the superoxide anion and pathological glutamate release, and, in such a way, limit progression of brain infarction within ischemic penumbra. These new findings may be instrumental in developing new antioxidant therapies for treatment of stroke.

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“…9,13,15 Reduction of brain glutamate release after ischemia appears to be an important mechanism by both NF-B dependent and independent pathways. 9,11,12 Glutamate toxicity may additionally be reduced by aspirin-mediated inhibition of prostaglandin (PG) formation. Prostaglandins synthesized by COX enhance the release of glutamate from astrocytes.…”

Section: Citicolinementioning

confidence: 99%

Multifunctional Actions of Approved and Candidate Stroke Drugs

Minnerup

Schäbitz

2009

Neurotherapeutics

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Summary: Ischemic stroke causes brain damage by multiple pathways. Previous stroke trials have demonstrated that drugs targeting one or only a few of these pathways fail to improve clinical outcome after stroke. Drugs with multimodal actions have been suggested to overcome this challenge. In this review, we describe the mechanisms of action of agents approved for secondary prevention of ischemic stroke, such as antiplatelet, antihypertensive, and lipid-lowering drugs. These drugs exhibit considerable properties beyond their classical mechanisms, including neuroprotective and neuroregenerative properties. In addition, candidate stroke drugs currently studied in clinical phase III trials are described. Among these, albumin, hematopoietic growth factors, and citicoline have been identified as promising agents with multiple mechanisms. These drugs offer hope that additional treatment options for the acute phase after a stroke will become available in the near future.

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Neuroprotection and glutamate attenuation by acetylsalicylic acid in temporary but not in permanent cerebral ischemia

Cited by 38 publications

References 27 publications

Xenon Neuroprotection in Experimental Stroke

Xenon Neuroprotection in Experimental Stroke

The neuroprotective properties of the superoxide dismutase mimetic tempol correlate with its ability to reduce pathological glutamate release in a rodent model of stroke

Multifunctional Actions of Approved and Candidate Stroke Drugs

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