Extracellular Antioxidants and Amino Acids in the Cortex of the Rat: Monitoring by Microdialysis of Early Ischemic Changes

Landolt, Hans; Lutz, T.; Langemann, Helen; Stäuble, D.; Mendelowitsch, Aminadav; Gratzl, O.; Honegger, C. G.

doi:10.1038/jcbfm.1992.12

Cited by 88 publications

(32 citation statements)

References 20 publications

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“…Under normal physiologic conditions, neurologic damages mediated by ROS can be prevented by the cellular antioxidant network. However, AsA levels decrease in the brain and rise sharply in extracellular fluid of the brain after severe ischemic hypoxia (Hillered et al, 1988;Landolt et al, 1992). The nitroxide radical by itself is also an antioxidant and can be used as a superoxide dismutase mimic Figure 6 The quantification of oxidized and total (oxidized + reduced) MC-P in brain tissue and blood using X-band EPR.…”

Section: Discussionmentioning

confidence: 99%

Brain Redox Imaging Using Blood—Brain Barrier-Permeable Nitroxide MRI Contrast Agent

Hyodo

Chuang

Goloshevsky

et al. 2008

J Cereb Blood Flow Metab

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Reactive oxygen species (ROS) and compromised antioxidant defense may contribute to brain disorders such as stroke, amyotrophic lateral sclerosis, etc. Nitroxides are redox-sensitive paramagnetic contrast agents and antioxidants. The ability of a blood-brain barrier (BBB)-permeable nitroxide, methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (MC-P), as a magnetic resonance-imaging (MRI) contrast agent for brain tissue redox imaging was tested. MC-P relaxation in rodent brain was quantified by MRI using a fast Look-Locker T 1 -mapping sequence. In the cerebral cortex and thalamus, the MRI signal intensity increased up to 50% after MC-P injection, but increased only by 2.7% when a BBB-impermeable nitroxide, 3CxP (3-carboxy-2,2,5,5,5-tetramethylpyrrolidine-1-oxyl) was used. The maximum concentrations in the thalamus and cerebral cortex after MC-P injection were calculated to be 1.9±0.35 and 3.0±0.50 mmol/L, respectively. These values were consistent with the ex vivo data of brain tissue and blood concentration obtained by electron paramagnetic resonance (EPR) spectroscopy. Also, reduction rates of MC-P were significantly decreased after reperfusion following transient MCAO (middle cerebral artery occlusion), a condition associated with changes in redox status resulting from oxidative damage. These results show the use of BBB-permeable nitroxides as MRI contrast agents and antioxidants to evaluate the role of ROS in neurologic diseases.

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Section: Discussionmentioning

confidence: 99%

Brain Redox Imaging Using Blood—Brain Barrier-Permeable Nitroxide MRI Contrast Agent

Hyodo

Chuang

Goloshevsky

et al. 2008

J Cereb Blood Flow Metab

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“…Glutathione efflux from brain cells is increased by potassium depolarization, iron (Fe 2+ ), inhibitors of mitochondrial respiration (malonate, 1-methyl-4-phenylpyridinium (MPP + ), 3-nitropropionic acid and cyanide), and after ischemia (32)(33)(34)(35)(36)(37)(38). In a previous study, we showed that the NMDA-mediated glutathione efflux was dependent on extracellular calcium but unrelated to dantrolene sensitive intracellular calcium release, osmotic change and glutathione-, or nitric oxide-synthesis (39).…”

Section: Introductionmentioning

confidence: 99%

Searching for Mechanisms of N-Methyl-d-Aspartate-Induced Glutathione Efflux in Organotypic Hippocampal Cultures

et al. 2003

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N-Methyl-D-aspartate (NMDA)-receptor stimulation evoked a selective and partly delayed elevated efflux of glutathione, phosphoethanolamine, and taurine from organotypic rat hippocampus slice cultures. The protein kinase inhibitors H9 and staurosporine had no effect on the efflux. The phospholipase A 2 inhibitors quinacrine and 4-bromophenacyl bromide, as well as arachidonic acid, a product of phospholipase A 2 activity, did not affect the stimulated efflux. Polymyxin B, an antimicrobal agent that inhibits protein kinase C, and quinacrine in high concentration (500 μM), blocked efflux completely. The stimulated efflux after but not during NMDA incubation was attenuated by a calmodulin antagonist (W7) and an anion transport inhibitor (DNDS). Omission of calcium increased the spontaneous efflux with no or small additional effects by NMDA. In conclusion, NMDA receptor stimulation cause an increased selective efflux of glutathione, phosphoethanolamine and taurine in organotypic cultures of rat hippocampus. The efflux may partly be regulated by calmodulin and DNDS sensitive channels.

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“…Diese Beobachtung wird auch durch eine tierexperimentelle Studie an Schafen bestätigt: Neben einer geringen Astrogliose mit vereinzelten Makrophagen entlang des Einstichkanals der Mikrodialysesonden fand sich nur in einem Fall ein kleines (10 mm×1,5 mm), subkortikales Hämatom [54]. In anderen tierexperimentellen Studien dieser Methode war es sogar schwierig,die Lage des Katheters selbst unter Anwendung entsprechender Färbungen überhaupt zu lokalisieren [29]. Im Vergleich mit intraparenchymalen oder intraventrikulären ICPSonden sind die verursachten Läsionen minimal, sodass die Anlage einer Mikrodialysesonde sicher und ethisch vertretbar ist, insbesondere bei Patienten, die ohnehin ein ICP-Monitoring oder eine Kraniotomie erhalten sollen [33].…”

Section: Sicherheit Der Methodeunclassified

Zerebrale Mikrodialyse beim Schlaganfall

Berger

Dohmen²,

Maurer

et al. 2004

Der Nervenarzt

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Cerebral microdialysis is an invasive technique for neurochemical monitoring that has been established for neuro-critical disorders such as subarachnoid hemorrhage and severe brain injury. We present data on cerebral microdialysis in stroke patients which were obtained in an ongoing study supported by the German Ministry for Education and Research. So far, 50 patients have been included who required critical care due to massive stroke of the middle cerebral artery territory. By correlating the microdialysis results with follow-up CT scans, we could define the neurochemical characteristics of three different brain compartments: (1) noninfarcted brain tissue with normal microdialysis values, (2) brain areas adjacent to the infarct core which were not hypodense in CT scans but caused reversible neurochemical alterations, and (3) the infarct core with massive concentration changes which did not normalize over the measuring period of 3 to 5 days. Microdialysis values averaged over time and correlated with initial PET scans helped to describe neurochemical predictors of a malignant, i.e., life-threatening, space-occupying course of the ischemic stroke. We discuss the value of this method in guiding therapy and predicting clinical outcome in the context of other neurological critical care disorders and describe the pros and cons of cerebral microdialysis as an invasive monitoring technique.

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Extracellular Antioxidants and Amino Acids in the Cortex of the Rat: Monitoring by Microdialysis of Early Ischemic Changes

Cited by 88 publications

References 20 publications

Brain Redox Imaging Using Blood—Brain Barrier-Permeable Nitroxide MRI Contrast Agent

Brain Redox Imaging Using Blood—Brain Barrier-Permeable Nitroxide MRI Contrast Agent

Searching for Mechanisms of N-Methyl-d-Aspartate-Induced Glutathione Efflux in Organotypic Hippocampal Cultures

Zerebrale Mikrodialyse beim Schlaganfall

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