A remarkable increase in total homocysteine concentrations in the CSF of migraine patients with aura.

OBJECTIVE: To investigate whether total and free homocysteine (HC) levels are increased in the cerebrospinal fluid (CSF) of patients with migraine headache compared with normal control populations. METHODS: The concentrations of free and total HC in the CSF of migraine without aura (MOA) and migraine with aura (MWA) patients were determined. RESULTS: The concentration of free HC did not differ significantly from normal controls, but the total HC concentration was significantly higher in MOA and MWA patients (41% increase in MOA, P < .001 and 376% increase in MWA, P < .0001) in the mean of the confidence interval of each groups compared with normal controls). CONCLUSIONS: These findings suggest that an increase of total HC concentration in the brain is commonly seen in migraine patient and is particularly pronounced in MWA sufferers. We speculate that total HC not only contribute to the development of atherosclerotic conditions, including cardiocerebrovascular diseases, but also reflects an epiphenomenon.

Decrease in asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in cerebrospinal fluid during elderly aging and in patients with sporadic form of amyotrophic lateral sclerosis.

BACKGROUND: Oxidative stress has been implicated in nervous system aging and the pathogenesis of amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. However, the effect of asymmetrical dimethylarginine (ADMA) was previously unknown. OBJECTIVE: We aimed to investigate the significance of nitric oxide (NO)-mediated neuronal death during elderly aging and in ALS. To do so, the concentration of ADMA, an endogenous NO synthase inhibitor in the cerebrospinal fluid (CSF), was determined in neurologically normal controls and in patients with ALS. MATERIALS AND METHODS: There were 20 untreated patients with ALS (M/F, 12/8) and 20 age-matched controls (M/F, 9/11), with a mean age (±SD) of 66.9 ± 9.2 years for patients and 65.1 ± 13.9 years for controls. The concentrations of ADMA and L-arginine (Arg) in the CSF of ALS patients were measured by high-performance liquid chromatography using an electrochemical detector. Control subjects were neurologically normal patients who underwent lumbar spinal anesthesia for minor surgery. RESULTS: The ADMA concentration significantly decreased with age, whereas the Arg concentration was unaltered. In patients with ALS, the ADMA concentration was significantly decreased compared with controls of a similar age (-52%, p = 0.0001). It significantly decreased with decreasing global functions of ALS (r(s) = -0.74, p < 0.005), whereas the Arg concentration did not change. CONCLUSION: These findings suggest that ADMA may play an important role in regulating NO synthesis in the nervous systems of the elderly during aging and in ALS.

L-Dopa therapy increases homocysteine concentration in cerebrospinal fluid from patients with Parkinson's disease.

To investigate the effect of L-3,4-dihydroxyphenylalanine (L-dopa) therapy on homocysteine (HC) concentration in patients with Parkinson's disease (PD), the concentrations in cerebrospinal fluid (CSF) of total HC and methionine (Met) were compared between 18 patients with PD before and after treatment with L-dopa and 16 neurologically normal control patients. Concentrations of total HC in patients with PD were significantly higher following L-dopa therapy (169+/-27 nM) than before treatment (111+/-22 nM) and than in controls (85+/-25 nM) (patients with PD before L-dopa treatment vs. controls, p<0.005; patients with PD after L-dopa treatment vs. before treatment, p<0.0001). Conversely, concentrations of total Met in patients with PD were significantly lower after L-dopa therapy (5.3+/-1.7 microM) than before L-dopa therapy (6.8+/-1.9 microM) (p<0.001). These findings in patients with PD suggest that L-dopa therapy enhances intracerebral methylation and elevates concentration of HC.

Levels of reduced and oxidized coenzyme Q-10 and 8-hydroxy-2'-deoxyguanosine in the cerebrospinal fluid of patients with living Parkinson's disease demonstrate that mitochondrial oxidative damage and/or oxidative DNA damage contributes to the neurodegenerative process.

The aim of this study was to investigate the possibility that mitochondrial oxidative damage, oxidative DNA damage or both contribute to the neurodegenerative process of Parkinson's disease (PD). We employed high-performance liquid chromatography (HPLC) using an electrochemical detector to measure concentrations of the reduced and oxidized forms of coenzyme Q-10 (CoQ-10) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the cerebrospinal fluid (CSF) of 20 patients with PD and 20 age-matched controls with no neurological disease. The percentage of oxidized to total CoQ-10 (%CoQ-10) in the CSF of the PD group (80.3+/-17.9%) was significantly higher than in the control group (68.2+/-20.4%, P<0.05). In addition, the concentration of 8-OHdG in the CSF of PD patients was greater than in the CSF of controls (P<0.0001) and was positively correlated with the duration of illness (r(s)=0.87, P<0.001). Finally, the %CoQ-10 was correlated with concentrations of 8-OHdG in the CSF of PD patients (r(s)=0.56, P<0.01). The present study suggests that both mitochondrial oxidative damage and oxidative DNA damage play important roles in the pathogenesis of early PD development.

Levels of reduced and oxidized coenzyme Q-10 and 8-hydroxy-2'-deoxyguanosine in the CSF of patients with Alzheimer's disease demonstrate that mitochondrial oxidative damage and/or oxidative DNA damage contributes to the neurodegenerative process.

To investigate the possibility that mitochondrial oxidative damage, oxidative DNA damage or both contribute to the neurodegenerative process of Alzheimer's disease (AD), we employed high-performance liquid chromatography using an electrochemical detector to measure the concentrations of the reduced and oxidized forms of coenzyme Q-10 (CoQ-10) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the cerebrospinal fluid (CSF) of 30 patients with AD and in 30 age-matched controls with no neurological disease. The percentage of oxidized/total CoQ-10 (%CoQ-10) in the CSF of the AD group (78.2 +/- 18.8%) was significantly higher than in the control group (41.3 +/- 10.4%) (P < 0.0001). The concentration of 8-OHdG in the CSF of AD patients was greater than in the CSF of controls (P < 0.0001) and was positively correlated with the duration of illness (r(s) = 0.95, P < 0.0001). The %CoQ-10 was correlated with concentrations of 8-OHdG in the CSF of AD patients (r(s) = 0.66, P < 0.001). The present study suggests that both mitochondrial oxidative damage and oxidative DNA damage play important roles in the pathogenesis of early AD development.

Homocysteine may contribute to pathogenesis of RNA damage in brains with Alzheimer's disease.

BACKGROUND: The pathogenesis of Alzheimer's disease (AD) is related to homocysteine (HC), but the details are unknown. OBJECTIVE: We aimed to measure the cerebrospinal fluid (CSF) concentrations of 8-hydroxyguanosine (8-OHG), considering RNA oxidative damage marker, free HC and total HC in the CSF of patients with AD and in normal control subjects. METHOD AND PATIENTS: Subjects were 18 untreated patients with AD (M/F = 7/11) and 15 age-matched controls (M/F = 9/6), with a mean age +/- SD of 67.4 +/- 5.0 years for patients and of 65.7 +/- 9.2 years for controls. The concentrations of free HC, total HC and 8-OHG in the CSF of AD patients were measured by high-performance liquid chromatography using an electrochemical detector. The control subjects were neurologically normal patients who underwent lumbar spinal anesthesia for minor surgery. RESULTS: Total HC and 8-OHG concentrations were significantly increased, and there was a significant positive correlation between total HC and 8-OHG concentrations. However, the concentration of 8-OHG in the CSF showed no correlation with 8-OHG in serum and was not significantly altered in AD patients. CONCLUSION: These results suggest that total HC and 8-OHG are positively correlated and may be related to AD pathogenesis due to RNA-associated oxidative damage linked to total HC.

Increase in the oxidized/total coenzyme Q-10 ratio in the cerebrospinal fluid of Alzheimer's disease patients.

BACKGROUND/AIM: The contribution of mitochondrial dysfunction and oxidative stress to the pathogenesis of Alzheimer's disease (AD) has previously been described. We aimed to investigate whether the balance between the oxidized and reduced forms of coenzyme Q-10 (CoQ-10) is related to the pathogenesis of AD. MATERIALS AND METHOD: Thirty patients with AD (69.0 +/- 4.1 years) and 30 healthy control subjects (63.8 +/- 16.4 years) were enrolled in this study. Concentrations of oxidized CoQ-10 and reduced CoQ-10 were measured by high-performance liquid chromatography using an electrochemical detector. RESULTS: The percentage of oxidized/total CoQ-10 in the cerebrospinal fluid (%CoQ-10, CSF) was significantly higher in the untreated AD group (78.2 +/- 18.8%) than in the control group (41.3 +/- 10.4%, p < 0.001), and there was a significant negative correlation between %CoQ-10 and the duration of the illness (r(s) = -0.93, p < 0.001). CONCLUSION: These findings in living AD patients suggest a possible role for %CoQ-10 in the pathogenesis of the early stage of AD development.

Remarkable increase in 3-nitrotyrosine in the cerebrospinal fluid in patients with lacunar stroke.

The goal of our study was whether free radicals contribute to the pathogenesis of the lacunar stroke to investigate the day after hospitalization, the concentrations of 3-nitrotyrosine and tyrosine in the cerebrospinal fluid (CSF) from living patients. The subjects included 20 living patients with lacunar stroke and 20 controls. The NIH stroke scale score was used to assess the severity of the stroke, including that the patients were mild cases. There was no expansion of the infarct lesion in the brain, as assessed by CT on the day following admission. The concentration of 3-nitrotyrosine was significantly higher in patients with lacunar stroke. In contrast, the concentration of tyrosine did not differ between the two groups. Furthermore, the 3-nitrotyrosine/tyrosine ratio was significantly higher in patients with lacunar stroke than in controls. Our results show that free radicals are produced in the CSF of lacunar stroke patients and that nitration of neuronal proteines is enhanced under this condition. These obsetvations suggest that lacunar stroke patients should be treated with edaravon, which is a free radical scavenger usually prescribed for cases of major strokes, as it will likely improve the prognosis of these patients.

Increase of oxidized/total coenzyme Q-10 ratio in cerebrospinal fluid in patients with Parkinson's disease.

The concentrations of oxidized coenzyme Q-10 (CoQ-10) and reduced CoQ-10 in the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD) was examined in order to determine whether the balance in oxidized and reduced CoQ-10 is related to the pathogenesis of PD. The percentage of oxidized/total CoQ-10 (%CoQ-10) in the CSF was significantly higher in the untreated PD group (80.3+/-17.9%) compared to the normal control group (68.2+/-20.4%) (p<0.05). The %CoQ-10 in the CSF of PD patients showed significant negative correlation with the duration of illness. These findings in living patients provide in vivo evidence for a possible role for %CoQ-10 in the pathogenesis in the early stages of PD development.

Increase of total homocysteine concentration in cerebrospinal fluid in patients with Alzheimer's disease and Parkinson's disease.

We determined the concentrations of free homocysteine (HC) and total HC in the cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) or Parkinson's disease (PD) in order to elucidate whether HC is related to the pathogenesis of these neurodegenerative diseases. The concentration of free HC did not differ significantly from that of the normal controls, while the concentration of total HC was significantly higher in the AD and PD patients (+31% in AD,+31% in PD; p<0.05). These findings suggest that an increase of total HC concentration in the brain is commonly seen in patients with AD and PD, and this may be related to the pathogenesis of these two diseases.

Alteration of 8-hydroxyguanosine concentrations in the cerebrospinal fluid and serum from patients with Parkinson's disease.

In order to investigate the possible role of oxidative RNA damage in the pathogenesis of Parkinson's disease (PD), the concentrations of the oxidative stress marker 8-hydroxyguanosine (8-OHG) were measured in the cerebrospinal fluid (CSF) and the serum of patients with PD and control subjects. The concentration of 8-OHG in CSF in PD patients was approximately three-fold that in controls (P < 0.001). The concentration of 8-OHG in CSF decreased significantly with the duration of disease (r(s) = -0.46, P < 0.05). However, the concentration of 8-OHG in serum was not significantly altered in PD patients compared to that in controls. In addition, the concentration of 8-OHG in CSF showed no correlation with that in serum in both the controls and PD patients suggesting that the 8-OHG concentrations in the CSF do not reflect those in serum and may be probably reflect those in brain tissue. These in vivo findings suggest a possible role of 8-OHG and increased oxidative RNA damage in the early stage of the development of PD.

Remarkable increase in the concentration of 8-hydroxyguanosine in cerebrospinal fluid from patients with Alzheimer's disease.

To investigate the possible role of oxidative RNA damage in the pathogenesis of Alzheimer's disease (AD), the concentrations of the oxidative stress marker 8-hydroxyguanosine (8-OHG) were measured in the cerebrospinal fluid (CSF) and the serum of patients with AD and control subjects. The concentration of 8-OHG in CSF in AD patients was approximately fivefold that in controls (P < 0.001). The concentration of 8-OHG in CSF decreased significantly with the duration of illness (r(s) = -0.48, P < 0.05) and the progression of cognitive dysfunctions (r(s) = 0.67, P < 0.01). However, the concentration of 8-OHG in CSF showed no correlation with that in serum in both the controls and AD patients. In addition, the concentration of 8-OHG in serum was not significantly altered in AD patients compared to that in controls, suggesting that the 8-OHG concentrations in the CSF do not reflect those in serum and may be probably reflect those in brain tissue. These in vivo findings suggest a possible role of 8-OHG and increased oxidative RNA damage in the early stage of the development of AD.