Lipid Peroxidation and Antioxidant Consumption as Early Markers of Neurosurgery-Related Brain Injury in Children.

BACKGROUND AND AIMS: Lipid peroxidation represents a marker of secondary brain injury both in traumatic and in non-traumatic conditions-as in major neurosurgical procedures-eventually leading to brain edema amplification and further brain damage. Malondialdehyde (MDA), a lipid peroxidation marker, and ascorbate, a marker of antioxidant status, can represent early indicators of this process within the cerebrospinal fluid (CSF). We hypothesized that changes in cerebral lipid peroxidation can be measured ex vivo following neurosurgery in children. METHODS: Thirty-six children (M:F = 19/17, median age 32.9 months; IQR 17.6-74.6) undergoing neurosurgery for brain tumor removal were admitted to the pediatric intensive care unit (PICU) in the postoperative period with an indwelling intraventricular catheter for intracranial pressure monitoring and CSF drainage. Plasma and CSF samples were obtained for serial measurement of MDA, ascorbate, and cytokines. RESULTS: An early brain-limited increase in lipid peroxidation was measured, with a significant increase from baseline of MDA in CSF (p = 0.007) but not in plasma. In parallel, ascorbate in CSF decreased (p = 0.05). Systemic inflammatory response following brain surgery was evidenced by plasma IL-6/IL-8 increase (p 0.0022 and 0.0106, respectively). No correlation was found between oxidative response and tumor site or histology (according to World Health Organization grading). Similarly, lipid peroxidation was unrelated to the length of surgery (mean 321 ± 73 min), or intraoperative blood loss (mean 20.9 ± 16.8% of preoperative volemia, 44% given hemotransfusions). Median PICU stay was 3.5 days (IQL range 2-5.5 d.), and postoperative ventilation need was 24 h (IQL range 20-61.5 h). The elevation in postoperative MDA in CSF compared with preoperative values correlated significantly with postoperative ventilation need (P = 0.05, r2 0168), while no difference in PICU stay was recorded. CONCLUSIONS: Our results indicate that lipid peroxidation increases consistently following brain surgery, and it is accompanied by a decrease in antioxidant defences; intraventricular catheterization offers a unique chance of oxidative process monitoring. Further studies are needed to evaluate whether monitoring post-neurosurgical oxidative stress in CSF is of prognostic utility.

Association of Nutrients with Biomarkers of Alzheimer's Disease.

Prospective cohort studies, cross-sectional surveys, autopsy studies and intervention clinical trials that investigated the association between nutrients and Alzheimer's disease (AD) have been reviewed. To estimate the relationship between specific nutrient intake and the risk of AD, Cochrane Library, PubMed, EMBASE, and the Fisher Center for Alzheimer's Research Foundation were searched for this purpose. Most published observational studies found an inverse relationship between vitamins, n-3 fatty acids and AD. The majority of intervention studies support the beneficial effect of combined vitamins and n-3 fatty acids providing them in the early stages of the disease. Only vitamin E and Zn supplementation failed to show any significant difference on the study population. On the other hand, high dietary intake of saturated fat and brain metal accumulation were positively associated with the incidence of AD.

Increased levels of ascorbic acid in the cerebrospinal fluid of cognitively intact elderly patients with major depression: a preliminary study.

Major depressive disorder (MDD) in the elderly is a risk factor for dementia, but the precise biological basis remains unknown, hampering the search for novel biomarkers and treatments. In this study, we performed metabolomics analysis of cerebrospinal fluid (CSF) from cognitively intact elderly patients (N = 28) with MDD and age- and gender-matched healthy controls (N = 18). The CSF levels of 177 substances were measured, while 288 substances were below the detection limit. Only ascorbic acid was significantly different, with higher levels in the MDD group at baseline. There were no correlations between CSF ascorbic acid levels and clinical variables in MDD patients at baseline. At the 3-year follow-up, there was no difference of CSF ascorbic acid levels between the two groups. There was a negative correlation between CSF ascorbic acid and CSF amyloid-ß42 levels in all subjects. However, there were no correlations between ascorbic acid and other biomarkers (e.g., amyloid-ß40, total and phosphorylated tau protein). This preliminary study suggests that abnormalities in the transport and/or release of ascorbic acid might play a role in the pathogenesis of late-life depression.

Distribution of vitamin C is tissue specific with early saturation of the brain and adrenal glands following differential oral dose regimens in guinea pigs.

Vitamin C (VitC) deficiency is surprisingly common in humans even in developed parts of the world. The micronutrient has several established functions in the brain; however, the consequences of its deficiency are not well characterised. To elucidate the effects of VitC deficiency on the brain, increased knowledge about the distribution of VitC to the brain and within different brain regions after varying dietary concentrations is needed. In the present study, guinea pigs (like humans lacking the ability to synthesise VitC) were randomly divided into six groups (n 10) that received different concentrations of VitC ranging from 100 to 1500 mg/kg feed for 8 weeks, after which VitC concentrations in biological fluids and tissues were measured using HPLC. The distribution of VitC was found to be dynamic and dependent on dietary availability. Brain saturation was region specific, occurred at low dietary doses, and the dose-concentration relationship could be approximated with a three-parameter Hill equation. The correlation between plasma and brain concentrations of VitC was moderate compared with other organs, and during non-scorbutic VitC deficiency, the brain was able to maintain concentrations from about one-quarter to half of sufficient levels depending on the region, whereas concentrations in other tissues decreased to one-sixth or less. The adrenal glands have similar characteristics to the brain. The observed distribution kinetics with a low dietary dose needed for saturation and exceptional retention ability suggest that the brain and adrenal glands are high priority tissues with regard to the distribution of VitC.

In vivo vitamin C deficiency in guinea pigs increases ascorbate transporters in liver but not kidney and brain.

Moderate vitamin C (vitC) deficiency (plasma concentrations less than 23 µmol/L) affects as much as 10% of adults in the Western World and has been associated with an increased mortality in disease complexes such as cardiovascular disease and the metabolic syndrome. The distribution of vitC within the body is subjected to complex and nonlinear pharmacokinetics and largely depends on the sodium-dependent vitC-specific transporters, sodium-dependent vitamin C transporter 1 (SVCT1) and sodium-dependent vitamin C transporter 2 (SVCT2). Although currently not established, it is likely to expect that a state of deficiency may affect the expression of these transporters to preserve vitC concentrations in specific target tissues. We hypothesized that diet-induced states of vitC deficiency lead to alterations in the messenger RNA (mRNA) and/or protein expression of vitC transporters, thereby regulating vitC tissue distribution. Using guinea pigs as a validated model, this study investigated the effects of a diet-induced vitC deficiency (100 mg vitC/kg feed) or depletion (0 mg vitC/kg feed) on the expression of transporters SVCT1 and SVCT2 in selected tissues and the transport from plasma to cerebrospinal fluid (CSF). In deficient animals, SVCT1 was increased in the liver, whereas a decreased SVCT1 expression but increased SVCT2 mRNA in livers of depleted animals suggests a shift in transporter expression as response to the diet. In CSF, a constant plasma:CSF ratio shows unaltered vitC transport irrespective of dietary regime. The study adds novel information to the complex regulation maintaining vitC homeostasis in vivo during states of deficiency.

Ascorbic acid and the brain: rationale for the use against cognitive decline.

This review is focused upon the role of ascorbic acid (AA, vitamin C) in the promotion of healthy brain aging. Particular attention is attributed to the biochemistry and neuronal metabolism interface, transport across tissues, animal models that are useful for this area of research, and the human studies that implicate AA in the continuum between normal cognitive aging and age-related cognitive decline up to Alzheimer's disease. Vascular risk factors and comorbidity relationships with cognitive decline and AA are discussed to facilitate strategies for advancing AA research in the area of brain health and neurodegeneration.

Changes in vitamin C and oxidative stress status during the treatment of tuberculous meningitis.

BACKGROUND: Tuberculosis (TB) is associated with oxidative stress and is traditionally linked to vitamin C deficiency. OBJECTIVE: To evaluate the time course of the oxidative stress marker, malondialdehyde (MDA), and vitamin C status during the clinical treatment of tuberculous meningitis (TBM). METHOD: MDA and vitamin C reduction/oxidation (redox) status were spectrophotometrically measured at admission and during hospital treatment in cerebrospinal fluid (CSF) and serum from 27 TBM patients and 20 controls. RESULTS: Baseline CSF and serum MDA levels in TBM patients were higher than in controls (both P < 0.05), and remained elevated throughout the study. CSF MDA steadily increased from baseline 0.66 ± 0.24 mol/l to 1.02 ± 0.33 µmol/l at the end of the sixth week of treatment (P < 0.05), and then returned to baseline levels. Baseline CSF and serum total vitamin C were lower in TBM patients than in controls, but were soon normalised. CSF and serum ascorbate, reduced/oxidised vitamin C ratios and ascorbate CSF/serum ratio were markedly decreased in TBM patients (P < 0.05), and showed no improvement during treatment. CONCLUSION: These results indicate increased local and systemic oxidative stress, accompanied by impaired redox status, but not total vitamin C deficiency, which persisted during conventional clinical treatment of TBM.

Levels of 5-methyltetrahydrofolate and ascorbic acid in cerebrospinal fluid are correlated: implications for the accelerated degradation of folate by reactive oxygen species.

Deficiency of 5-methyltetrahydrofolate (5-MTHF) in cerebrospinal fluid (CSF) is associated with a number of neurometabolic conditions including mitochondrial electron transport chain defects. Whilst failure of the active transport of 5-methyltetrahydrofolate (5-MTHF) into the CSF compartment has been proposed as a potential mechanism responsible for the 5-MTHF deficiency seen in mitochondrial disorders, it is becoming increasingly clear that other mechanisms are involved. Here, we have considered the role of oxidative stress as a contributing mechanism. Concerning, ascorbic acid (AA), we have established a CSF reference range (103-303µM) and demonstrated a significant positive correlation between 5-MTHF and AA. Furthermore, CSF itself was also shown to convey antioxidant properties towards 5-MTHF. However, this protection could be overcome by the introduction of a hydroxyl radical generating system. Using a neuronal model system, inhibition of mitochondrial complex I, by 58%, was associated with a 23% increase in superoxide generation and a significantly increased loss of 5-MTHF from the extracellular medium. Addition of AA (150µM) was able to prevent this increased 5-MTHF catabolism. We conclude that increased generation of reactive oxygen species and/or loss of CSF antioxidants are also factors to consider with regard to the development of a central 5-MTHF deficiency. Co-supplementation of AA together with appropriate folate replacement may be of therapeutic benefit.

Measurement of total antioxidant capacity of human plasma: setting and validation of the CUPRAC-BCS method on routine apparatus ADVIA 2400.

BACKGROUND: Quantification of Total Antioxidant Capacity (TAC) of human plasma is an important clinical target, since many diseases are suspected to be related with oxidative stress. The CUPRAC-BCS (BCS=Bathocuproinedisulfonic acid) method was chosen since it works using the photometric principle, with stable and inexpensive reagents and at physiological pH. METHODS: The method is based on the complex equilibria between Cu(II)-BCS (reagent) and Cu(I)-BCS. Cu(I)-BCS complex is formed by reducing ability of the plasma redox active substances. The photometric signal is achieved at 478 nm and calibration is performed using urate as a reference substance. RESULTS: Linearity, linear working range, sensitivity, precision, LoD, LoQ, selectivity and robustness have been considered to validate the method. Absorbance at 478 nm was found linear from 0.0025 up to 2.0 mmol L(-1) of urate reference solution. Precision was evaluated as within-day repeatability, Sr=4 µmol L(-1), and intermediate-precision, SI(T)=15 µmol L(-1). LoD and LoQ, resulted equal to 7.0 µmol L(-1) and 21 µmol L(-1) respectively while robustness was tested having care for pH variation during PBS buffer preparation. Tests on plasma (80 samples) and on human cerebrospinal fluid (30 samples) were conducted and discussed. CONCLUSIONS: By the analytical point of view, the photometric method was found to be simple, rapid, widely linear and reliable for the routine analysis of a clinical laboratory. By the clinical point of view, the method response is suitable for the study of chemical plasma quantities related to redox reactivity.

Amorphous carbon nitride as an alternative electrode material in electroanalysis: simultaneous determination of dopamine and ascorbic acid.

Boron-doped diamond (BDD) films are excellent electrode materials, whose electrochemical activity for some analytes can be tuned by controlling their surface termination, most commonly either to predominantly hydrogen or oxygen. This tuning can be accomplished by e.g. suitable cathodic or anodic electrochemical pretreatments. Recently, it has been shown that amorphous carbon nitride (a-CNx) films may present electrochemical characteristics similar to those of BDD, including the influence of surface termination on their electrochemical activity toward some analytes. In this work, we report for the first time a complete electroanalytical method using an a-CNx electrode. Thus, an a-CNx film deposited on a stainless steel foil by DC magnetron sputtering is proposed as an alternative electrode for the simultaneous determination of dopamine (DA) and ascorbic acid (AA) in synthetic biological samples by square-wave voltammetry. The obtained results are compared with those attained using a BDD electrode. For both electrodes, a same anodic pretreatment in 0.1 mol L(-1) KOH was necessary to attain an adequate and equivalent separation of the DA and AA oxidation potential peaks of about 330 mV. The detection limits obtained for the simultaneous determination of these analytes using the a-CNx electrode were 0.0656 µmol L(-1) for DA and 1.05 µmol L(-1) for AA, whereas with the BDD electrode these values were 0.283 µmol L(-1) and 0.968 µmol L(-1), respectively. Furthermore, the results obtained in the analysis of the analytes in synthetic biological samples were satisfactory, attesting the potential application of the a-CNx electrode in electroanalysis.

A dual-template imprinted polymer-modified carbon ceramic electrode for ultra trace simultaneous analysis of ascorbic acid and dopamine.

A dual-template imprinted polymer film containing dispersed multiwalled carbon nanotubes was exploited in the fabrication of a typical, reproducible, and rugged carbon ceramic electrode, adopting "surface grafting from" approach for the growth of a nanometer thin coating on its surface. For this, chloro groups were first introduced at the exterior surface of silica-carbon composite electrode through sol-gel modification using (3-chloropropyl)-trimethoxysilane, followed by an iniferter (sodium diethyl dithiocarbamate) initiated photopolymerization of functional monomer (2,4,6-trisacrylamido-1,3,5-triazine), mixed templates (ascorbic acid and dopamine), and cross-linker (ethylene glycol dimethacrylate), in the presence of multiwalled carbon nanotubes. The modified sensor was validated for the simultaneous analysis of ascorbic acid and dopamine in aqueous, blood serum, cerebrospinal fluid, and pharmaceutical samples, using differential pulse anodic stripping voltammetric technique. The oxidation peak potentials for both analytes were found to be well apart approximately by 300 mV, which was large enough to allow selective and sensitive analysis of one in the presence of other, without any cross reactivity, interferences and false-positives. The detection limits realized by the proposed sensor, under optimized conditions, were found to be as low as 2.24 ng mL(-1) for ascorbic acid and 0.21 ng mL(-1) for dopamine (S/N=3). Such stringent limits could be considered suitable for the primitive diagnosis of several chronic diseases, in clinical settings.

1H-NMR-based metabolomic profiling of CSF in early amyotrophic lateral sclerosis.

BACKGROUND: Pathophysiological mechanisms involved in amyotrophic lateral sclerosis (ALS) are complex and none has identified reliable markers useful in routine patient evaluation. The aim of this study was to analyze the CSF of patients with ALS by (1)H NMR (Nuclear Magnetic Resonance) spectroscopy in order to identify biomarkers in the early stages of the disease, and to evaluate the biochemical factors involved in ALS. METHODOLOGY: CSF samples were collected from patients with ALS at the time of diagnosis and from patients without neurodegenerative diseases. One and two-dimensional (1)H NMR analyses were performed and metabolites were quantified by the ERETIC method. We compared the concentrations of CSF metabolites between both groups. Finally, we performed principal component (PCA) and discriminant analyses. PRINCIPAL FINDINGS: Fifty CSF samples from ALS patients and 44 from controls were analyzed. We quantified 17 metabolites including amino-acids, organic acids, and ketone bodies. Quantitative analysis revealed significantly lower acetate concentrations (p = 0.0002) in ALS patients compared to controls. Concentration of acetone trended higher (p = 0.015), and those of pyruvate (p = 0.002) and ascorbate (p = 0.003) were higher in the ALS group. PCA demonstrated that the pattern of analyzed metabolites discriminated between groups. Discriminant analysis using an algorithm of 17 metabolites revealed that patients were accurately classified 81.6% of the time. CONCLUSION/SIGNIFICANCE: CSF screening by NMR spectroscopy could be a useful, simple and low cost tool to improve the early diagnosis of ALS. The results indicate a perturbation of glucose metabolism, and the need to further explore cerebral energetic metabolism.

Uric acid as a CNS antioxidant.

Oxidative damage is a consistent finding in a number of central nervous system (CNS) disorders. Uric acid (UA) is a potent hydrophilic antioxidant that is modified by diet and drug. Several lines of evidence suggest that plasma UA may modulate outcomes in neurologic disease, but little attention has been paid to CNS levels of UA. Our objective was to test the hypothesis that cerebrospinal fluid (CSF) UA is determined by plasma UA, modified by blood-brain barrier (BBB) integrity and associated with rate of cognitive decline in Alzheimer's disease (AD). Also, since UA and ascorbic acid may act as antioxidants for one another, we also explored a potential interaction between them in the brain. Thirty-two patients with mild to moderate AD (Mini-Mental Status Exam 19 +/- 5) participated in a longitudinal biomarker study for one year involving standardized clinical assessments. CSF and blood were collected at baseline for UA, ascorbic acid, and albumin. Cognitive measures were collected at baseline and again one year later. CSF UA was independent of age, gender, and AD severity. CSF and plasma UA were positively correlated (r=0.669, p=0.001) and BBB impairment was associated with higher CSF levels of UA (p=0.028). Neither plasma nor CSF UA reached significant association with rates of cognitive decline over 1 year. CSF UA and CSF ascorbic acid were positively correlated (r=0.388, p=0.001). The hypothesis that CSF UA is determined by plasma UA and BBB integrity is supported, as is the hypothesis that UA and ascorbic acid are associated in CSF but not plasma. Adequately powered prospective studies would help assess any role for UA in primary and secondary prevention of AD.

Prevention of symptomatic vasospasm by continuous cisternal irrigation with mock-CSF containing ascorbic acid and Mg(2+).

BACKGROUND: Symptomatic vasospasm (SVS) is still a major cause of poor outcome in cases undergoing early surgical intervention for ruptured intracranial aneurysm. Among the numbers of therapeutic trials to prevent and ameliorate neurological deterioration due to SVS, removal or quenching of oxy-hemoglobin (OxyHb) from subarachnoid colts and administration of Mg(2+) (Mg) have especially been expected to be effective. In this report the authors investigated the effect of continuous cisternal irrigation (CCI) with mock CSF containing ascorbic acid (ASA) and Mg, performed after early surgery for ruptured aneurysm. METHOD: Sixty-three cases which had received CCI were retrospectively compared with 40 control cases as to the incidence of SVS and outcome. FINDINGS: Incidence of SVS was significantly less frequent (P < 0.05) in the CCI group (11%) than in the control group (25%). Severe and definitive SVS requiring additional specific treatment occurred only in 3.2% of the CCI group, while 22.5% in the control (P < 0.01). Overall outcome at discharge was significantly better in the CCI group than in the control (P < 0.01). CONCLUSIONS: Postoperative CCI with ASA and Mg was definitively effective in preventing SVS and in lessening severity of SVS if it occurs.

Oxidative stress in cerebrospinal fluid of patients with aseptic and bacterial meningitis.

This study aimed to determine whether patients with aseptic and bacterial meningitis presented alterations in oxidative stress parameters of cerebrospinal fluid (CSF). A total of 30 patients were used in the research. The CSF oxidative stress status has been evaluated through many parameters, such as lipid peroxidation through thiobarbituric acid reactive substances (TBARS) and antioxidant defense systems such as superoxide dismutase (SOD), glutathione S-transferase (GST), reduced glutathione (GSH) and ascorbic acid. TBARS levels, SOD and GST activity increase in aseptic meningitis and in bacterial meningitis. The ascorbic acid concentration increased significantly in patients with both meningitis types. The reduced glutathione levels were reduced in CSF of patients with aseptic and bacterial meningitis. In present study we may conclude that oxidative stress contributes at least in part to the severe neurological dysfunction found in meningitis.

Ascorbic acid and rates of cognitive decline in Alzheimer's disease.

The brain maintains high levels of ascorbic acid (AA) despite a concentration gradient favoring diffusion from brain to peripheral tissues. Dietary antioxidants, including AA, appear to modify the risk of Alzheimer's disease (AD). The objective of this study was to test the hypothesis that neurodegeneration in AD is modified by brain levels of AA. Thirty-two patients with mild to moderate AD participated in a biomarker study involving standardized clinical assessments over one year. Cerebrospinal fluid (CSF) and serum were collected at baseline for AA and albumin content. Cognitive measures were collected at baseline and one year. CSF and plasma AA failed to predict cognitive decline independently, however, CSF: plasma AA ratio did. After adding CSF Albumin Index (an established marker of blood-brain barrier integrity) to the regression models the effect of CSF: plasma AA ratio as a predictor of cognitive decline was weakened. CSF: plasma AA ratio predicts rate of decline in AD. This relationship may indicate that the CSF: plasma AA ratio is an index of AA availability to the brain or may be an artifact of a relationship between blood-brain barrier impairment and neurodegeneration.

[Serum and cerebrospinal fluid concentration of vitamins A, E and C in patients with tick-borne encephalitis]. / Stezenie witamin A, E oraz C w surowicy krwi i plynie mózgowo-rdzeniowym chorych z kleszczowym zapaleniem mózgu--doniesienie wstepne.

We included in our study 18 patients hospitalized because of tick borne encephalitis (tbc) at the Departament of Infectious Diseases and Neuroinfections of Medical University of Bialystok. In this group, concentration of vitamins A, E and C in serum and cerebrospinal fluid (CSF) was measured before and after treatment. The control group consisted of 11 patients with no inflammatory changes in CSF were observed. We did not observe significant differences in concentration of vitamins in serum and CSF before and after treatment comparing to controls. However, we showed significant increase in concentration of vitamin E before and after treatment in both serum and CSF in patients with tbc in comparison with control group.

Total antioxidant/oxidant status in meningism and meningitis.

The objective of this study was to investigate the antioxidant/oxidant status of serum and cerebrospinal fluid in children with meningismus and acute bacterial meningitis. Twenty-three children (age range, 0.75 to 9 years) with fever and meningeal signs that required analysis of the cerebrospinal fluid, but no cytologic or biochemical evidence of meningitis in their serum and cerebrospinal fluid, constituted the meningismus group. Thirty-one children (age range, 0.5 to 10 years) with acute bacterial meningitis constituted the meningitis group. Twenty-nine healthy children (age range, 0.5 to 11 years) were recruited as control subjects. Antioxidant status (ascorbic acid, albumin, thiol, uric acid, total bilirubin, total antioxidant capacity, catalase and ceruloplasmin concentrations) and oxidant status (lipid hydroperoxide and total oxidant status) were measured. The serum antioxidant status was lower, and oxidant status levels higher in both meningitis and meningismus subjects than in the control children (P < 0.001). Cerebrospinal fluid oxidant status was lower in the meningitis group than in the meningismus group (P < 0.05). These results indicate that serum antioxidant status was lower, and serum oxidant status was higher in children in the meningismus and meningitis groups, whereas cerebrospinal fluid oxidant status was higher in the meningismus group than in the meningitis group.

Age-dependent change in Vitamin C status: a phenomenon of maturation rather than of ageing.

Several reports have shown that Vitamin C is depleted in animals with age. Based mainly on comparisons between young animals that have not yet reached maturity and old animals, it appears to be the general assumption that the change in Vitamin C status occurs at a late stage in life and that this phenomenon may either contribute to or result from the ageing process. In the present study, young (3 months old, n = 8) and old (36 months old, n = 8) female guinea pigs were followed for 6 months with monthly blood samplings and monitored for Vitamin C status as measured by plasma ascorbate and erythrocyte ascorbate recycling capacity after which the animals were euthanized. While remaining unchanged in the old animals, plasma Vitamin C status of the young animals significantly declined to that of the old animals within 3 months. During the following 3 months, the Vitamin C status of the young animals remained unchanged. Furthermore, post mortem Vitamin C analyses of the animals now aged 9 and 42 months, respectively, showed no effect of age on Vitamin C in plasma, liver, kidney, heart and brain between the groups while concentrations were significantly increased in cerebrospinal fluid and lung with age (p < 0.05). Moreover, a significantly elevated ascorbic acid oxidation ratio was observed in young compared to old animals (p < 0.05). The present data suggest that the decline in Vitamin C status with age occur early in life and is a phenomenon of maturation rather than of ageing. Data from other species and humans are discussed.

Influence of repetitive transcranial magnetic stimulation on disease severity and oxidative stress markers in the cerebrospinal fluid of patients with spinocerebellar degeneration.

Ataxia severity, cerebellar hemispheric blood flow (CHBF), ascorbate free radical (AFR), superoxide dismutase protein, superoxide scavenging activity, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in cerebrospinal fluid (CSF) were compared before and after an 8-week course of repetitive transcranial magnetic stimulation (rTMS) in 20 patients with spinocerebellar degenerations (SCD). SCD patients showed higher AFR, 8-OHdG, and superoxide scavenging activity than 19 controls. In SCD patients, AFR and ataxia severity declined, and CHBF increased after rTMS. As the SCD patients showed negative correlations between ataxia severity and CHBF or superoxide scavenging activity, the therapeutic mechanism of rTMS may involve decreased oxidative stress and increased CHBF.