Levels of low molecular weight scavengers in the rat brain during focal ischemia

Lyrer, Philippe; Landolt, Hans; Kabiersch, Alexa; Langemann, Helen; Kaeser, H E

doi:10.1016/0006-8993(91)90811-9

Cited by 64 publications

(19 citation statements)

References 12 publications

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“…With total tissue levels of 2 -3 m M (Lyrer et al, 1991;Uemura et al, 1991;Rice et al, 1995), ascorbate and GSH are 10-20 times more concentrated cysteine and 500-1000 times higher than uric acid (Lyrer et al, 1991;Uemura et al, 1991).…”

Section: Ascorbate a N D Gsh As Antioxidantsmentioning

confidence: 99%

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Ascorbate compartmentalization in the CNS

Rice

1999

neurotox res

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Ascorbic acid, found physiologically as the ascorbate anion, is an abundant water-soluble antioxidant. It is concentrated in the intracellular compartment of all tissues in the body. The CNS has particularly high levels of ascorbate. Recent data from this laboratory indicate that ascorbate is distinctly compartmentalized between neurons and glia, with an average intracellular concentration of 10 mM in neurons and 1 mM in glial cells. These data can be contrasted with those for another important low molecular weight antioxidant, glutathione, which is somewhat more concentrated in glia than in neurons. The present review summarizes evidence for ascorbate compartmentalization between neurons and glia and considers these data in light of evidence for the roles of ascorbate as a neuroprotective antioxidant and as a neuromodulator in the CNS.

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Section: Ascorbate a N D Gsh As Antioxidantsmentioning

confidence: 99%

“…Ascorbic acid, the ascorbate anion at physiological pH, is one of the most abundant low molecular weight antioxidants in the CNS (Lyrer et al, 1991). Ascorbate is not synthesized in brain cells, but rather its cellular levels are maintained by active uptake.…”

Section: Introductionmentioning

confidence: 99%

Ascorbate compartmentalization in the CNS

Rice

1999

neurotox res

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“…This approach offers the opportunity to measure GSH content in live animals. The GSH antioxidant system can be activated when the brain is under oxidative stress, such as during the reperfusion period after an ischemic insult when GSH demand may be relatively higher (70,71). It will also be affected by many neurological disorders, such as Parkinson disease (72) and Alzheimer disease (73).…”

Section: Mcb Labeling With Two-photon Microscopy Resolves Cellular Gsmentioning

confidence: 99%

Two-photon Imaging of Glutathione Levels in Intact Brain Indicates Enhanced Redox Buffering in Developing Neurons and Cells at the Cerebrospinal Fluid and Blood-Brain Interface

Sun

Shih

Johannssen

et al. 2006

Journal of Biological Chemistry

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Glutathione is the major cellular thiol present in mammalian cells and is critical for maintenance of redox homeostasis. However, current assay systems for glutathione lack application to intact animal tissues. To map the levels of glutathione in intact brain with cellular resolution (acute tissue slices and live animals), we have used two-photon imaging of monochlorobimane fluorescence, a selective enzyme-mediated marker for reduced glutathione. Previously, in vitro experiments using purified components and cultured glial cells attributed cellular monochlorobimane fluorescence to a glutathione S-transferase-dependent reaction with GSH. The tripeptide glutathione (GSH; ␥-L-glutamyl-L-cysteinylglycine) is the most abundant low molecular weight thiol in mammalian cells and constitutes a major cellular defense against reactive oxygen species. Deficiency in the GSH system has been linked to neuronal loss during progression of neurodegenerative diseases, such as Parkinson, Alzheimer, Huntington, and amyotrophic lateral sclerosis (1-3), as well as acute conditions such as spinal cord injury (4) and stroke (5-7). Although reactive oxygen species accumulation has been implicated in these disorders, examination of GSH levels in previous studies has largely been restricted to enzymatic assays and fluorescent probes that are only applicable in neuronal and glial cell cultures or brain homogenates. A widely used method for measuring GSH in cultured cells and tissue homogenates employs monochlorobimane (MCB) 4 (8), a normally nonfluorescent dye that when conjugated to reduced GSH by intracellular glutathione S-transferases (GSTs) forms adducts that can be measured fluorometrically. Recently, investigators have established that GSH in epidermal cells of intact Arabidopsis roots can be elegantly and quantitatively measured by two-photon laser scanning microscopy (TPLSM) with MCB (9). Accordingly, we now use a similar approach in intact mammalian brain to directly monitor GSH levels in different tissues.Data on GSH concentrations in different brain areas of various species obtained using chemical techniques have been summarized (10). However, because these results were derived from tissue homogenates, they only provide information on the average GSH content. It is also conceivable that other techniques such as thiol-reactive probes (11) may lack specificity for GSH or suffer from the disposition of thiols/ GSH changing in response to animal sacrifice and/or fixation. Furthermore, studies from cultured brain cells are potentially affected by media constituents that contain high levels of GSH precursors such as cystine, present at 100 M in minimal essential media but less than 1 mM in cerebrospinal fluid in vivo (12). Here we show that MCB is a specific probe for GSH labeling in brain tissues, and TPLSM can be used to image GSH content in various brain regions at the cellular level. In our assay, the extracellular environment contains a large reservoir of MCB (compared with intracellular GSH), and therefore the reaction between M...

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“…15 In this respect, GUA is considered one of the major sources of uric acid in the brain. After cerebral ischemia and TBI, uric acid levels are increased 16,17 and it is an important antioxidant in the body. It has been demonstrated that a great amount of release of purine nucleotides and nucleosides occurs in central nervous system disorders, such as trauma, ischemia, and hypoxia, from neurons and astrocytes.…”

Section: Discussionmentioning

confidence: 99%

Superoxide Dismutase, Catalase, and Guanase in Traumatic Brain Injury

Kuçur

Tanrıverdi

Dashti

et al. 2005

Neurosurgery Quarterly

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Objectives: Reactive oxygen species generated after brain trauma trigger a cascade of events resulting in neuronal death. Despite numerous defenses, the brain is vulnerable to oxidative damage, mainly because of its high content of unsaturated fatty acids. The goal in this experimental study was to demonstrate the activities of antioxidant enzymes, namely, superoxide dismutase, catalase, and guanase, in plasma and brain tissue at 30 minutes and 60 minutes after brain trauma.Methods: Forty adult male Sprague-Dawley rats were used as subjects. Rats in group 1 were subjected to moderate head injury, whereas rats in group 2 were subjected to severe head injury. Eight rats served as a sham operated (control) group. Results:The results of this study showed that there is, in general, an increase in the activities of these 3 enzymes in plasma; however, in the brain tissue, we observed that guanase activities were decreased during the posttraumatic period.Conclusion: These alterations in enzyme activities suggest that lipid peroxidation ensues in the early period of trauma and that treatment strategies aimed to increase antioxidant enzyme activities may prevent the secondary mechanisms resulting in neuronal death.

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Levels of low molecular weight scavengers in the rat brain during focal ischemia

Cited by 64 publications

References 12 publications

Ascorbate compartmentalization in the CNS

Ascorbate compartmentalization in the CNS

Two-photon Imaging of Glutathione Levels in Intact Brain Indicates Enhanced Redox Buffering in Developing Neurons and Cells at the Cerebrospinal Fluid and Blood-Brain Interface

Superoxide Dismutase, Catalase, and Guanase in Traumatic Brain Injury

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