Nitric oxide as an activity marker in multiple sclerosis

Nitric oxide (NO) molecules have one of the most important roles in the pathogenesis of multiple sclerosis (MS). It has been stated that a continuous and high concentration of NO metabolites in CSF and in the serum of MS patients in relapse may cause toxic damage to myelin and oligodendroglia. The aim of this study was to investigate whether NO is a marker of disease activity and is correlated with other disease activity markers such as active lesions on brain magnetic resonance imaging (MRI) and increased immunoglobulin G (IgG) index. Cerebrospinal fluid (CSF) and peripheral serum (PS) samples were taken from patients with definite MS (n = 24) during relapse and remission and from control subjects (n = 18). The Griess reaction was used to measure the NO metabolites, nitrite and nitrate in CSF and PS. Cranial MRI was carried out with triple dose (0,3 mmol/kg) gadolinium and the IgG index was determined. Nitrite and nitrate concentrations (NNCs) of CSF were 11.16 +/- 8.60 micromol/ml in relapse and 6.72 +/- 3.50 micromol/ml in remission, whereas in PS they were 12.89 +/- 7.62 micromol/ml during relapse and 12.35 +/- 6.62 micromol/ml during remission. In control subjects NNCs in CSF and PS were 7.42 +/- 2.81 micromol/ml and 4.37 +/- 1.63 micromol/ml respectively. NNCs in CSF during relapse period were significantly higher than those of both remission phase and control subjects (p = 0.000). Although serum NNCs did not differ in relapse and remission, they were still higher than normal controls. Validity analysis revealed that NNC measurement in CSF was 71 % specific and 66 % sensitive to disease activity. The most important result was the significant correlation of increased NNCs with the existence of active lesion in cranial MRI and an increase in IgG index (p < 0.05).In conclusion, these results add background data to assist in further outlining the possible role of NO in the pathogenesis of MS. Together with the other markers it may be used as an activity marker in relapses of MS.     

Role of nitric oxide in cerebral blood flow abnormalities after traumatic brain injury.

Nitric oxide (NO) has important regulatory functions within the central nervous system. NO is oxidized in vivo to nitrate and nitrite (NO(x)). Measurement of these products gives an index of NO production. The purpose of this study was to examine the relation between the brain extracellular concentration of NO metabolites and cerebral blood flow (CBF) after severe traumatic brain injury. Using a chemiluminescence method, NO(x) concentrations were measured in 6,701 microdialysate samples obtained from 60 patients during the first 5 d after severe head injury. Regional and global values of CBF obtained by xenon-enhanced computed tomography were used for analyses. Dialysate NO(x) values were the highest within the first 24 h after brain trauma and gradually decreased over the 5 postinjury d (time effect, P < 0.001). Mean dialysate concentration of NO(x) was 15.5 +/- 17.6 micromol/L (minimum 0.3, maximum 461 micromol/L) and 65% of samples were between 5 and 20 micromol/L. There was a significant relation between regional CBF and dialysate NO(x) levels (r2 = 0.316, P < 0.001). Dialysate NO(x) levels (9.5 +/- 2.2 micromol/L) in patients with critical reduction of regional CBF (<18 mL. 100 g-1. min-1) were significantly lower than in patients with normal CBF (18.6 +/- 8.1 micromol/L; P < 0.001). This relation between the dialysate concentration of NO(x) and regional CBF suggests some role for NO in the abnormalities of CBF that occur after traumatic brain injury.     

Is there a role for nitric oxide activity in cervicogenic headache?

Cervicogenic headache (CEH) is a unilateral headache that can be provoked by neck movement, awkward head positions or pressure on tender points in the neck. The mechanisms underlying the stimulation of pain in CEH are not clearly known. In this study, we measured serum nitrate and nitrite levels as an index of nitric oxide (NO) activity in 15 patients with CEH during headache and headache-free periods and in 15 healthy controls. Total nitrate+nitrite levels were found to be higher in CEH patients during headache periods than in healthy controls (20.7+/-3.8 micromol/l vs 14.4+/-3.6 micromol/l, p<0.001), but not in CEH patients during headache-free periods (16.1+/-2.2 micromol/l) compared with the controls (p>0.05). In the patients with CEH, serum total nitrate+nitrite levels were found to be higher during headache periods than during headache-free periods (p=0.001). It can thus be hypothesized that the changes observed are a cause of the attack rather than a consequence of the disease process.     

Cerebrospinal fluid nitrite/nitrate correlated with oxyhemoglobin and outcome in patients with subarachnoid hemorrhage

The findings of various studies reporting temporal changes in CSF total nitrite/nitrate (NOx) levels after subarachnoid hemorrhage (SAH) vary considerably. The study group comprised 10 patients with SAH and 10 control subjects. Total nitrite/nitrate concentration was measured by a vanadium-based assay with the colorimetric Griess reaction. CSF oxyhemoglobin level was assessed by spectrophotometry. After an initial peak (22.6+/-10.1 microM) within first 24 h after SAH, CSF NOx decreased gradually during the period of observation. There was a significant correlation between CSF concentrations of NOx and OxyHb in the entire observation period (R=0.87, p<0.001). When the impact of bleeding into CSF was considered, patients with very good outcome [Glasgow Outcome Scale (GOS)=5] had significantly lower CSF NOx (11.1+/-1.3 microM) than those with worse outcome (GOS<5) (21.8+/-11.2 microM, p<0.01). In conclusion, this study demonstrates that after aneurysm rupture CSF NOx levels correlate with OxyHb. We suggest this as a novel interpretation of other variable findings in relation to NO metabolites in the central nervous system (CNS) post SAH, and hence it could usefully be incorporated into the planning of future studies, correlating NOx with clinical outcome.     

Increased S-nitrosothiols and S-nitrosoalbumin in cerebrospinal fluid after severe traumatic brain injury in infants and children: indirect association with intracranial pressure.

Nitric oxide (NO) is implicated in both secondary damage and recovery after traumatic brain injury (TBI). Transfer of NO groups to cysteine sulfhydryls on proteins produces S-nitrosothiols (RSNO). S-nitrosothiols may be neuroprotective after TBI by nitrosylation of N-methyl-D-aspartate receptor and caspases. S-nitrosothiols release NO on decomposition for which endogenous reductants (i.e., ascorbate) are essential, and ascorbate is depleted in cerebrospinal fluid (CSF) after pediatric TBI. This study examined the presence and decomposition of RSNO in CSF and the association between CSF RSNO level and physiologic parameters after severe TBI. Cerebrospinal fluid samples (n = 72) were obtained from 18 infants and children on days 1 to 3 after severe TBI (Glasgow Coma Scale score < 8) and 18 controls. Cerebrospinal fluid RSNO levels assessed by fluorometric assay peaked on day 3 versus control (1.42 +/- 0.11 micromol/L vs. 0.86 +/- 0.04, P< 0.05). S-nitrosoalbumin levels were also higher after TBI (n = 8, 0.99 +/- 0.09 micromol/L on day 3 vs. n = 6, 0.42 +/- 0.02 in controls, P< 0.05). S-nitrosoalbumin decomposition was decreased after TBI. Multivariate analysis showed an inverse relation between CSF RSNO and intracranial pressure and a direct relation with barbiturate treatment. Using a novel assay, the presence of RSNO and S-nitrosoalbumin in human CSF, an approximately 1.7-fold increase after TBI, and an association with low intracranial pressure are reported, supporting a possible neuroprotective role for RSNO. The increase in RSNO may result from increased NO production and/or decreased RSNO decomposition.     

Raised cerebrospinal fluid nitrite and nitrate levels in patients with multiple sclerosis: no correlation with disease activity

A growing body of evidence implicates excessive generation of nitric oxide (NO) within the central nervous system (CNS) in multiple sclerosis (MS). The aim of our study is to analyse nitrite and nitrate as end products of NO in the cerebrospinal fluid (CSF) from MS patients and correlate the concentrations with clinicol characteristics of the disease. CSF nitrite and nitrate concentrations were measured after reduction of nitrate, by Griess reaction, in 105 MS potients, 27 patients with non-inflammatory neurological disorders (NIND) and 13 individuals without neurological disorder (Co). Mean CSF nitrite and nitrate concentrations were significantly higher in patients with MS and NIND compared with the Co patients (9.44 and 8.68, respectively, versus 6.85 microM; P=0.0001 and P=0.031, respectively). There was no significant correlation between CSF nitrite and nitrate concentrations and activity, phase, severity and duration of MS. Our data are in agreement with the results of previous studies which have demonstrated raised concentrations of CSF NO metabolites in MS patients, providing further evidence for NO involvement in MS. The lack of correlation between NO metabolites and disease activity speaks in favour of the possible dual role of NO, as both immunoregulatory and pro-inflammatory molecule, in the pathogenesis of MS.     

Relation of cerebral energy metabolism and extracellular nitrite and nitrate concentrations in patients after aneurysmal subarachnoid hemorrhage.

In a prospective clinical investigation on neurochemical intensive care monitoring, the authors' aim was to elucidate the temporal profile of nitric oxide metabolite concentrations-that is, nitrite and nitrate (NO(x))--and compounds related to energy-metabolism in the cerebral interstitium of patients after aneurysmal subarachnoid hemorrhage (SAH). During aneurysm surgery, microdialysis probes were implanted in cerebral white matter of the vascular territory most likely affected by vasospasm. Temporal profiles of NO(x) were analyzed in a subset of 10 patients (7 female, 3 male, mean age = 47 +/- 14 years). Microdialysis was performed for 152 +/- 63 hours. Extracellular metabolites (glucose, lactate, pyruvate, glutamate) were recovered from the extracellular fluid of the cerebral parenchyma. NO(x) was measured using a fluorometric assay. After early surgery, SAH patients revealed characteristic decreases of NO(x) from initial values of 46.2 +/- 34.8 micromol/L to 23.5 +/- 9.0 micromol/L on day 7 after SAH (P < 0.05). Decreases in NO(x) were seen regardless of development of delayed ischemia (DIND). Overall NO(x) correlated intraindividually with glucose, lactate, and glutamate (r = 0.58, P < 0.05; r = 0.32, P < 0.05; r = 0.28, P < 0.05; respectively). After SAH, cerebral extracellular concentrations of NO metabolites decrease over time and are associated with concomitant alterations in energy-or damage-related compounds. This could be related to reduced NO availability, potentially leading to an imbalance of vasodilatory and vasoconstrictive factors. On the basis of the current findings, however, subsequent development of DIND cannot be explained by a lack of vasodilatory NO alone.     

Endogenous melatonin increases in cerebrospinal fluid of patients after severe traumatic brain injury and correlates with oxidative stress and metabolic disarray

Oxidative stress plays a significant role in secondary damage after severe traumatic brain injury (TBI); and melatonin exhibits both direct and indirect antioxidant effects. Melatonin deficiency is deleterious in TBI animal models, and its administration confers neuroprotection, reducing cerebral oedema, and improving neurobehavioural outcome. This study aimed to measure the endogenous cerebrospinal fluid (CSF) and serum melatonin levels post-TBI in humans and to identify relationships with markers of oxidative stress via 8-isoprostaglandin-F2alpha (isoprostane), brain metabolism and neurologic outcome. Cerebrospinal fluid and serum samples of 39 TBI patients were assessed for melatonin, isoprostane, and various metabolites. Cerebrospinal fluid but not serum melatonin levels were markedly elevated (7.28+/-0.92 versus 1.47+/-0.35 pg/mL, P<0.0005). Isoprostane levels also increased in both CSF (127.62+/-16.85 versus 18.28+/-4.88 pg/mL, P<0.0005) and serum (562.46+/-50.78 versus 126.15+/-40.08 pg/mL (P<0.0005). A strong correlation between CSF melatonin and CSF isoprostane on day 1 after injury (r=0.563, P=0.002) suggests that melatonin production increases in conjunction with lipid peroxidation in TBI. Relationships between CSF melatonin and pyruvate (r=0.369, P=0.049) and glutamate (r=0.373, P=0.046) indicate that melatonin production increases with metabolic disarray. In conclusion, endogenous CSF melatonin levels increase after TBI, whereas serum levels do not. This elevation is likely to represent a response to oxidative stress and metabolic disarray, although further studies are required to elucidate these relationships.     

Serum nitrite and nitrate levels in epileptic children using valproic acid or carbamazepine

In experimental epilepsy studies, nitric oxide was found to act as both proconvulsant and anticonvulsant. The objective of this study was to investigate the effects of valproic acid and carbamazepine on serum levels of nitrite and nitrate, which are the metabolites of nitric oxide. To achieve this goal, serum nitrite and nitrate levels were determined in active epileptic 34 children using valproic acid and 23 children using carbamazepine and in non-active epileptic 38 children (control group) not using any antiepileptic drug. In the valproic acid group serum nitrite and nitrate levels were 2.66 +/- 2.11 micromol/l and 69.35 +/- 23.20 micromol/l, 1.89 +/- 1.01 micromol/l and 49.39 +/- 10.61 micromol/l in the carbamazepine group, and 1.22 +/- 0.55 micromol/l, 29.53 +/- 10.05 micromol in the control group, respectively. Nitrite and nitrate levels were significantly high in both valproic acid and carbamazepine groups compared to the control group (P < 0.01). When valproic acid and carbamazepine groups were compared to each other, level of nitrate was found statistically higher in the valproic acid group in relation to the carbamazepine group (P < 0.01), however, there was no statistically significant difference in the levels of nitrite (P > 0.05). No relation could be found between serum drug levels and nitrite and nitrate levels. According to these results, it can be suggested that valproic acid and carbamazepine might have antiepileptic effects through nitric oxide.     

No changes in cerebrospinal fluid levels of nitrite, nitrate and cyclic GMP with aging

Summary Nitric oxide (NO) is a free radical gas that plays a role in various signal transduction processes. NO has been proposed to have a function in the mechanism of synaptic plasticity, including long-term potentiation and memory formation in vivo. Because a failure in synaptic plasticity is considered to be involved in aging-associated brain dysfunction, NO production in the brain may be altered by aging. In the present study, we measured the levels of NO metabolites, nitrite and nitrate, and cyclic GMP in the cerebrospinal fluid (CSF) of human subjects without neurological or psychiatric disorders. There were no age-related changes in the CSF levels of either nitrite, nitrate or cyclic GMP. These results suggest that NO production in the brain may be maintained during the aging process.     

Low concentration of nitrite and nitrate in the cerebrospinal fluid from schizophrenic patients: a pilot study

Some evidence suggests a dysfunctional nitric oxide (NO) system in the brain of schizophrenic subjects. We measured the concentrations of the stable metabolites of NO, nitrite, and nitrate in the cerebrospinal fluid (CSF) from schizophrenic and control patients with other neurological disorders and found lowered levels in the schizophrenic group as compared with the control group. This finding supports the hypothesis of a NO system reduction in the brain of schizophrenic subjects.     

Reduced plasma nitric oxide metabolites before and after antipsychotic treatment in patients with schizophrenia compared to controls

BACKGROUND: Nitric oxide (NO) is believed to have a role in the pathophysiology of schizophrenia. We examined plasma levels of NO metabolites in patients with schizophrenia and normal controls. We also determined the impact of 6-week risperidone treatment on circulating NO metabolites in patients with schizophrenia. METHOD: Plasma NO metabolite (NO(x)) levels were measured in 55 schizophrenia patients before and after 6-week treatment with risperidone and in 55 normal controls. Severity of schizophrenia and response to treatment were assessed with the positive and negative syndrome scale (PANSS) for schizophrenia. NO(x) levels were estimated by the Griess method. RESULTS: Pre-treatment plasma NO(x) levels in schizophrenia patients (8.97+/-6.74 micromol/L) were lower than those of normal controls (14.51+/-6.30 micromol/L) (p<0.01). Schizophrenia patients had lower post-treatment NO(x) levels (10.99+/-8.31 micromol/L) than those of normal controls (p<0.01). There was marginal significant change between plasma NO(x) levels before and after 6-week treatment (p=0.056). Moreover, in 37 treatment responders (>/=30% improvement in PANSS score), post-treatment plasma NO(x) significantly increased in comparison to pre-treatment NO(x) (p=0.028). CONCLUSIONS: Plasma levels of NO(x) in patients with schizophrenia were significantly lower than normal controls both before and after the treatment. Our findings suggest that the improvement of psychiatric symptoms can lead to partially normalize a deficiency of NO after treatment in schizophrenia patients. Our findings support the hypothesis that the NO system is dampened in schizophrenia.     

Increased nitric oxide radicals in postmortem brain from patients with schizophrenia

Alterations in antioxidant status in schizophrenia suggest free radical-mediated neurotoxicity; this finding can be a consequence of increased free radical production. There are multiple pathways to excess free radical generation and subsequent oxidative stress. One such pathway is the formation of peroxynitrite by a reaction of nitric oxide (NO) and superoxide radical. NO is formed from L-arginine by nitric oxide synthase (NOS). A constitutive cytosolic isoform, neuronal NOS (nNOS), appears to be fairly stable in the postmortem brain tissues. Utilizing a sensitive fluorometric assay, NO levels were measured by its stable metabolites, nitrate and nitrite, in the caudate region of postmortem brain tissues from patients and control subjects. In the human brain, NO is metabolized primarily in the form of nitrate. A significantly increased level of NO was found in schizophrenia patients (241 +/- 146 pmol/mg dry weight, n = 18) than was found in those of normal (142 +/- 65 pmol/mg dry weight, n = 20) and psychiatric controls without schizophrenia (125 +/- 83 pmol/mg dry weight, n = 16) (analysis of covariance [ANCOVA], F = 6.446, df = 2,51, p = 0.003). These findings were independent of age, brain weight, postmortem interval (PMI), sample storage time, or cigarette smoking. Elevated NO levels in the brains of schizophrenia patients lend further support for the free radical pathology in schizophrenia.     

Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome

CSF and serum were obtained from 16 patients with idiopathic restless legs syndrome (RLS) and 8 age-matched healthy control subjects. Patients with RLS had lower CSF ferritin levels (1. 11 +/- 0.25 ng/mL versus 3.50 +/- 0.55 ng/mL; p = 0.0002) and higher CSF transferrin levels (26.4 +/- 5.1 mg/L versus 6.71 +/- 1.6 mg/L; p = 0.018) compared with control subjects. There was no difference in serum ferritin and transferrin levels between groups. The presence of reduced ferritin and elevated transferrin levels in CSF is indicative of low brain iron in patients with idiopathic RLS.     

Increased brain interstitial fluid adenosine concentration during hypoxia in newborn piglet

The effects of arterial hypoxia on interstitial fluid adenosine concentrations were studied in the frontal cortex and thalamus by the brain dialysis technique and in CSF from the cisterna magna of the newborn piglet. Acute hypoxia (PaO2 = 20 +/- 1 mm Hg) increased the interstitial fluid adenosine concentrations significantly from 0.68 +/- 0.29 (SEM) to 1.60 +/- 0.35 microM in the frontal cortex and from 1.03 +/- 0.32 to 2.60 +/- 0.86 microM in the thalamus (n = 8). Interstitial fluid inosine and hypoxanthine also increased significantly during hypoxia. In separate groups of piglets, the adenosine concentration in the cisterna magna CSF under normoxic conditions was 0.04 +/- 0.01 microM (n = 5), which increased significantly to 0.17 +/- 0.04 microM (n = 6) with hypoxia (PaO2 = 4.7 +/- 1.2 mm Hg). Cisterna magna CSF inosine levels did not change significantly during the severe hypoxia. Adenosine concentrations found in the interstitial space and CSF of newborn piglets under normoxic and hypoxic conditions are within the vasodilator range. These results thus suggest that in the neonatal brain adenosine may play a role in regulating blood flow during hypoxia.     

Detection of elastin derived peptides in cerebrospinal fluid of patients with first ever ischaemic stroke

OBJECTIVE: We have previously reported the optimized methods for the detection of elastin derived peptides (EDP) in the serum, synovial fluid, and bronchoalveolar lavage. The aim of the present study was to investigate whether EDP are detectable in cerebrospinal fluid (CSF) of patients with acute brain ischaemia. PATIENTS AND METHODS: Twenty-seven first ever ischaemic stroke patients (mean age 61.5+/-10.8 years; age range 47-70 years; 12 women) were studied in acute phase (1-15 days after the onset) with clinical evaluations, radiological assessments, and the analysis of serum and CSF based on Western blot and ELISA for the detection and quantification of EDP. RESULTS: None of the serum EDP concentrations are significantly higher in stroke patients compared with 25 healthy control individuals. However, EDP levels in CSF are strongly (p<0.0001) elevated compared with healthy subjects. They correlated with total cholesterol (r=0.53; p=0.02), triglycerides (r=0.67; p=0.004) and retinopathy (r=0.24; p=0.03), and with the interval between the stroke onset and the time of lumbar puncture (r=0.35; p=0.02). CONCLUSION: EDPs are detectable in CSF of healthy subjects and patients with ischaemic stroke. Acute brain infarction is followed by increased levels of EDP in CSF.     

Acute decrease in cerebral nitric oxide levels after subarachnoid hemorrhage.

Disturbances in the nitric oxide (NO) vasodilatory pathway have been implicated in acute vasoconstriction and ischemia after subarachnoid hemorrhage (SAH). The authors hypothesize that blood released during SAH leads to vasoconstriction by scavenging NO and limiting its availability. This was tested by measuring the major NO metabolites nitrite and nitrate in five different brain regions before and after experimental SAH. The basal NO metabolites levels were as follows (mean +/- SD, micromol/mg wet weight): brain stem, 0.14 +/- 0.07; cerebellum, 0.12 +/- 0.08; ventral convexity cortex, 0.22 +/- 0.15; dorsal convexity cortex, 0.16 +/- 0.11; and hippocampus, 0.26 +/- 0.17. In sham-operated animals, no effect of the nitric oxide synthase (NOS) inhibitor L(G)-nitro-L-arginine-methyl-ester (30 mg/kg) was found on NO metabolites 40 minutes after administration, but a significant decrease was seen after 120 minutes. The NO metabolites decreased significantly 10 minutes after SAH in all brain regions except for hippocampus, and recovered to control levels in cerebellum at 60 minutes and in brain stem and dorsal cerebral cortex 180 minutes after SAH, while remaining low in ventral convexity cortex. Nitrite recovered completely in all brain regions at 180 minutes after SAH, whereas nitrate remained decreased in brain stem and ventral convexity cortex. Our results indicate that SAH causes acute decreases in cerebral NO levels by a mechanism other than NOS inhibition and provide further support for the hypothesis that alterations in the NO vasodilatory pathway contribute directly to the ischemic insult after SAH.     

Nitric oxide-related brain damage in acute ischemic stroke

BACKGROUND AND PURPOSE: The neurotoxic and neuroprotective role of nitric oxide (NO) in experimental cerebral ischemia has generated considerable debate. The aim of this study was to analyze the relationship between NO metabolite (NO-m) concentrations in cerebrospinal fluid (CSF) and clinical and neuroimaging parameters of brain injury in patients with acute ischemic stroke. METHODS: We studied 102 patients and 24 control subjects who were included in a larger previous study conducted to analyze risk factors of progressing stroke. NO generation was calculated by quantifying nitrates and nitrites with a colorimetric assay in CSF samples obtained within the first 24 hours from symptoms onset. Early neurological deterioration was defined as a fall of 1 or more points in Canadian Stroke Scale score between admission and 48 hours after inclusion. Infarct volume was measured on days 4 to 7 by cranial CT. RESULTS: Median NO-m concentrations [quartiles] were 2.1 [1.0, 4.5] micromol/mL in patients and 1.0 [1.0, 1.0] micromol/mL in control subjects (P<0.0001). In 45 patients with subsequent early neurological deterioration, NO-m levels in CSF were significantly higher than in those with stable stroke (4.0 [1.7, 7.8] versus in 1. 6 [1.0, 2.5] micromol/mL, P<0.0001). There was a moderate correlation between NO-m and infarct volume (coefficient 0.39, P<0. 001). NO-m concentrations >5.0 micromol/mL were significantly associated with early neurological worsening (OR 5.7, 95% CI 1.2 to 27.4; P=0.030) independent of other important factors related to progressing stroke, such as CSF glutamate levels. CONCLUSIONS: Our clinical findings suggest an important role of NO generation in acute ischemic stroke. Increased NO-m in CSF are associated with a greater brain injury and early neurological deterioration.     

Nitric oxide metabolites and interleukin-6 in cerebrospinal fluid from multiple sclerosis patients

Interleukin-6 (IL-6) and nitric oxide (NO) are implicated in the pathology of multiple sclerosis (MS). We have investigated the levels of these mediators in the cerebrospinal fluid (CSF) from 50 patients with MS and 23 control subjects. Mean CSF IL-6 level was higher in the total MS group in comparison with controls, but not significantly, whilst the difference between patients with stable MS and controls reached the level of statistical significance. Mean CSF nitrite/nitrate level was significantly higher in the total MS group compared with the control group, as well as in active MS patients versus controls. There was significant difference neither in the mean CSF IL-6 nor in nitrite/nitrate levels between active and stable MS patients. Interestingly, we observed a significant negative correlation between IL-6 and nitrite/nitrate levels in the CSF in the total MS group. Such a trend existed in both subgroups with active and stable MS, but without reaching the level of statistical significance. Our data further support the involvement of IL-6 and NO in ongoing pathological processes in MS, suggesting their potential interplay within the central nervous system in this disease.     

Nitrite,nitrate and cGMP in the cerebrospinal fluid in degenerative neurologic diseases

Summary To investigate whether nitric oxide (NO) plays a role in degenerative neurologic disease (DND), we measured nitrite, nitrate and cyclic GMP in cerebrospinal fluid (CSF) samples from patients with Parkinson's disease (PD), spinocerebellar ataxia (SCA) and amyotrophic lateral sclerosis (ALS). We found no significant change in CSF nitrite, nitrate or cyclic GMP in patients with any DND compared with control values. These results suggest that NO production is preserved in PD, SCA and ALS.