Neurochemical analysis of focal ischemia in rats.

Uemura, Yoshiaki; Miller, Julie; Matson, Wayne R.; Beal, M. Flint

doi:10.1161/01.str.22.12.1548

Cited by 113 publications

(68 citation statements)

References 35 publications

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“…4 These increments have been attributed to the conversion of XDH to XO within the ischemic tissue 25,26 or within endothelial cells. 27 Uric acid also protected cultured rat hippocampal neurons against cell death induced by glutamate.…”

Section: Discussionmentioning

confidence: 99%

“…Ischemia also promotes the conversion of xanthine dehydrogenase (XDH) to xanthine oxidase (XO), as the likely result of increased intracellular calcium, and activation of proteases. 3,4 Whereas XDH activity does not produce reactive oxygen species, the XO reaction is a major source of free radicals during ischemia/reperfusion injury. 5 Arguing for a role of XO in brain damage are studies in which allopurinol, a XO inhibitor, has been shown to have protective effects against reperfusion injury.…”

mentioning

confidence: 99%

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Prognostic Significance of Uric Acid Serum Concentration in Patients With Acute Ischemic Stroke

Chamorro

Obach

Cervera

et al. 2002

Stroke

225

167

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Background and Purpose-We sought to assess in 881 consecutive patients with acute ischemic stroke the clinical relevance in regard to functional outcome of the natural antioxidant uric acid measured at hospital admission. Methods-Patients had serum uric acid (mg/dL) measured by standard procedures 18.2Ϯ15.5 hours from clinical onset.At hospital discharge (11.0Ϯ6.0 days), neurological impairment was classified as moderate/severe (Mathew score Յ75; nϭ304) or mild/absent (Mathew score Ͼ75; nϭ577). Demographics, atherosclerotic risk factors, history of organ disease, baseline neurological score, stroke subtype, infarction size, renal function, aspirin use before stroke, stroke therapy, diuretic use, and laboratory markers, including erythrocyte sedimentation rate, were analyzed in both outcome groups with the use of backward logistic regression. Results-Increased uric acid values were found in men, hypertensives, alcohol drinkers, and patients with coronary, pulmonary, or renal diseases. Diabetic patients had lower uric acid levels on admission. Uric acid was directly associated with hematocrit (Pϭ0.001), sodium (Pϭ0.001), creatinine (Pϭ0.001), and triglycerides (Pϭ0.001) and inversely related with nonfasting glucose (Pϭ0.001) levels. Neurological impairment on admission (Pϭ0.001) and final infarction size on CT/MRI (Pϭ0.01) were also inversely associated with uric acid. A logistic regression adjusted for confounders confirmed the following independent (odds ratio, 95% CI) good outcome predictors: age (0.97, 0.96 to 0.99), Mathew score on admission (1.14, 1.12 to 1.17), erythrocyte sedimentation rate (0.98, 0.97 to 0.99), infarction volume (0.98, 0.98 to 0.99), and uric acid (1.12, 1.00 to 1.25). Conclusions-In patients with acute ischemic stroke, there is a 12% increase in the odds of good clinical outcome for each milligram per deciliter increase of serum uric acid. This finding reinforces the relevance of oxidative damage in ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Prognostic Significance of Uric Acid Serum Concentration in Patients With Acute Ischemic Stroke

Chamorro

Obach

Cervera

et al. 2002

Stroke

225

167

View full text Add to dashboard Cite

show abstract

“…GUO presents neuroprotective effect in in vivo and in vitro experimental models of brain diseases associated with glutamatergic excitotoxicity [11,12]. It was showed that after focal stroke in rats, GUO levels are elevated within 2 h and remain high for 7 days in the brain tissue [13]. In oxygen/glucose deprivation (OGD) protocol, an in vitro model for ischemia, we showed that GUO is protective by improving extracellular glutamate uptake [14].…”

Section: Introductionmentioning

confidence: 95%

Guanosine prevents nitroxidative stress and recovers mitochondrial membrane potential disruption in hippocampal slices subjected to oxygen/glucose deprivation

Thomaz

Dal-Cim

Martins

et al. 2016

Purinergic Signalling

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Guanosine, the endogenous guanine nucleoside, prevents cellular death induced by ischemic events and is a promising neuroprotective agent. During an ischemic event, nitric oxide has been reported to either cause or prevent cell death. Our aim was to evaluate the neuroprotective effects of guanosine against oxidative damage in hippocampal slices subjected to an in vitro ischemia model, the oxygen/glucose deprivation (OGD) protocol. We also assessed the participation of nitric oxide synthase (NOS) enzymes activity on the neuroprotection promoted by guanosine. Here, we showed that guanosine prevented the increase in ROS, nitric oxide, and peroxynitrite production induced by OGD. Moreover, guanosine prevented the loss of mitochondrial membrane potential in hippocampal slices subjected to OGD. Guanosine did not present an antioxidant effect per se. The protective effects of guanosine were mimicked by inhibition of neuronal NOS, but not of inducible NOS. The neuroprotective effect of guanosine may involve activation of cellular mechanisms that prevent the increase in nitric oxide production, possibly via neuronal NOS.

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“…However, in most cases data linking the GSH system to these disorders were derived from tissue homogenates, which cannot detect cellular heterogeneity. It is possible that these limitations may have contributed to contrary reports on how the GSH levels change during some neurological diseases (75)(76)(77)(78). Our approach can be applied to animal models of disease and mouse mutants with abnormal handling of oxidative stress (79,80) to measure GSH levels in different brain regions directly.…”

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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Neurochemical analysis of focal ischemia in rats.

Cited by 113 publications

References 35 publications

Prognostic Significance of Uric Acid Serum Concentration in Patients With Acute Ischemic Stroke

Prognostic Significance of Uric Acid Serum Concentration in Patients With Acute Ischemic Stroke

Guanosine prevents nitroxidative stress and recovers mitochondrial membrane potential disruption in hippocampal slices subjected to oxygen/glucose deprivation

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

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