Cerebrospinal fluid hypoxanthine, xanthine and uric acid levels may reflect glutamate-mediated excitotoxicity in different neurological diseases

Stover, John; Lowitzsch, К.; Kempski, Oliver

doi:10.1016/s0304-3940(97)00840-9

Cited by 101 publications

(81 citation statements)

References 20 publications

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“…Oxidative stress and glutamate‐mediated excitotoxicity plays an important role in NMOSD pathogeny (Marignier et al., 2010). CSF UA levels could reflect oxidative stress and glutamate‐mediated excitotoxicity in neurological patients (Stover et al., 1997), and it has been suggested (Stover et al., 1997) that increasing oxidative stress is reflected by UA and elevated uric acid levels are associated with glutamate‐mediated excitotoxicity in CSF. Therefore, we speculated that NMOSD patients with impaired BBB, longer disease duration, active lesions upon MRI, or brain lesions suffered from greater oxidative stress and excitotoxicity.…”

Section: Discussionmentioning

confidence: 85%

“…It not only activates immune effectors in the innate and adaptive immune systems (Shi et al., 2003), but also enhances antibody immunity (Behrens et al., 2008). Some studies have also suggested that UA is a strong peroxynitrite scavenger and antioxidant (Hooper et al., 2000; Sevanian, Davies, & Hochstein, 1991; Waugh, 2008), while others have shown that UA reflects xanthine oxidase activity with its subsequent production of free radicals (Kanemitsu et al., 1989) and is associated with oxidative stress and glutamate‐mediated excitotoxicity in neurological patients (Stover, Lowitzsch, & Kempski, 1997). …”

Section: Introductionmentioning

confidence: 99%

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Elevated cerebrospinal fluid uric acid during relapse of neuromyelitis optica spectrum disorders

Shu

Zhang

et al. 2016

Brain and Behavior

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IntroductionPrevious studies have shown that serum uric acid (UA) modulates outcomes of neurological diseases, although little is known about cerebrospinal fluid (CSF) UA levels in neuromyelitis optica spectrum disorders (NMOSDs).MethodsCerebrospinal fluid and serum UA levels were measured in samples from 68 patients, including NMOSDs during relapse (n = 38) and controls with noninflammatory and non‐neurodegenerative diseases (CTLs, n = 30). Correlation analysis was performed between CSF UA and clinical characteristics, serum UA, and blood–brain barrier integrity in NMOSDs.ResultsCerebrospinal fluid UA levels in NMOSDs were significantly higher than in CTLs (p = .002), while serum UA differences between NMOSDs and CTLs were not statistically significant. In NMOSDs, CSF UA levels were significantly higher in patients with an impaired blood–brain barrier than in patients with an intact one (p < .001), and significantly higher in longer disease duration than in shorter disease duration patients (p = .002). CSF UA levels were also significantly higher in active patients upon MRI than in inactive patients (p < .001), and significantly higher in patients with brain lesions than without brain lesions (p = .024). CSF UA was significantly associated with the serum UA levels (r = .454, p = .002), disease duration (r = .383, p = .018), and blood–brain barrier index (r = .805, p < .001), but did not correlate with age, gender, annualized relapse rate, duration, or severity of NMOSD. Multiple regression analysis demonstrated that CSF UA was independent of the blood–brain barrier index (β = .765, p < .001) and serum UA levels (β = .01, p = .019) in NMOSDs.ConclusionsCerebrospinal fluid UA levels were elevated in NMOSD patients during relapse, and were likely modified by serum UA levels and blood–brain barrier integrity.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Elevated cerebrospinal fluid uric acid during relapse of neuromyelitis optica spectrum disorders

Shu

Zhang

et al. 2016

Brain and Behavior

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“…In a study of 34 MS patients and 20 controls with NIND, Stover et al found 2-3-fold increases in CSF UA concentrations in MS patients compared with controls (27). Additionally, Becker et al found normal UA concentrations in blood and CSF of 18 patients with MS (33).…”

Section: Discussionmentioning

confidence: 98%

“…Available data on CSF UA concentrations in MS patients is scarce and controversial. Previous studies show CSF UA concentrations in MS patients to be either increased (27), the same as in control patients (28), or reduced in MS patients compared with controls (29). Only one study has investigated CSF UA concentrations in relation to disease activity (28).…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid and serum uric acid levels in patients with multiple sclerosis

Dujmović¹,

Gazibara²,

Obrenović³

et al. 2009

Clinical Chemistry and Laboratory Medicine

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Background: Peroxynitrite was hypothesized to be involved in the pathogenesis of multiple sclerosis (MS) through its various neurotoxic effects. Uric acid (UA) was shown to be a strong peroxynitrite scavenger. Methods: We analyzed cerebrospinal fluid (CSF) and serum UA concentrations in 30 MS patients and 20 controls with non-inflammatory neurological diseases (NIND) and correlated these findings with demographic and clinical characteristics of MS patients. Disease activity was assessed by brain magnetic resonance imaging (MRI) and the CSF/serum albumin quotient as an indicator of the state of blood-brainbarrier (BBB). Results: Serum UA concentrations were found to be significantly lower in MS patients compared with controls (ps0.019). CSF UA concentrations were lower in MS patients as compared to controls, as well as in patients with active MS (clinical and/or MRI activity) in comparison to patients with inactive MS or controls, but these differences were not statistically significant. Significant correlation was found between CSF and serum UA concentrations (ps0.016) in MS patients, but not in controls; and between CSF UA concentrations and the CSF/serum albumin quotient in MS patients (ps0.043), but not in controls. Conclusions: Our results support the significance of UA in the pathogenesis of MS. Decreased serum UA concentrations in MS patients might be due to both intrinsically reduced antioxidant capacity and increased UA consumption in MS. CSF UA concentrations may not be a reliable marker of disease activity in MS since its concentration is dependent on leakage

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“…Accordingly, glutamate levels have been found to be significantly higher in the CSF (Stover et al, 1997;Sarchielli et al, 2003) and in the brains of MS patients (Srinivasan et al, 2005). Furthermore, glutamate clearance and receptor expression are impaired in MS brains (Pitt et al, 2000;Geurts et al, 2003Geurts et al, , 2005VallejoIllarramendi et al, 2006) and in animal models of the disease (Hardin-Pouzet et al, 1997;Pitt et al, 2000;Smith et al, 2000;Ohgoh et al, 2002), whereas glutamate receptor antagonists exert beneficial effects in experimental autoimmune encephalomyelitis (EAE) (Wallstrom et al, 1996;Bolton and Paul, 1997;Pitt et al, 2000;Smith et al, 2000) and in MS (Plaut, 1987) by limiting not only oligodendrocyte but also neuronal damage (Pitt et al, 2000;Smith et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Inflammation Triggers Synaptic Alteration and Degeneration in Experimental Autoimmune Encephalomyelitis

Centonze¹,

Muzio²,

Rossi³

et al. 2009

J. Neurosci.

349

420

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Neurodegeneration is the irremediable pathological event occurring during chronic inflammatory diseases of the CNS. Here we show that, in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, inflammation is capable in enhancing glutamate transmission in the striatum and in promoting synaptic degeneration and dendritic spine loss. These alterations occur early in the disease course, are independent of demyelination, and are strongly associated with massive release of tumor necrosis factor-␣ from activated microglia. CNS invasion by myelin-specific blood-borne immune cells is the triggering event, and the downregulation of the early gene Arc/Arg3.1, leading to the abnormal expression and phosphorylation of AMPA receptors, represents a culminating step in this cascade of neurodegenerative events. Accordingly, EAE-induced synaptopathy subsided during pharmacological blockade of AMPA receptors. Our data establish a link between neuroinflammation and synaptic degeneration and calls for early neuroprotective therapies in chronic inflammatory diseases of the CNS.

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Cerebrospinal fluid hypoxanthine, xanthine and uric acid levels may reflect glutamate-mediated excitotoxicity in different neurological diseases

Cited by 101 publications

References 20 publications

Elevated cerebrospinal fluid uric acid during relapse of neuromyelitis optica spectrum disorders

Elevated cerebrospinal fluid uric acid during relapse of neuromyelitis optica spectrum disorders

Cerebrospinal fluid and serum uric acid levels in patients with multiple sclerosis

Inflammation Triggers Synaptic Alteration and Degeneration in Experimental Autoimmune Encephalomyelitis

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