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Objectives: Impulsive behavior is the precursor of many psychiatric and neurological conditions. High levels of impulsive behavior will increase health risk behavior and related injuries. Impulsive behavior is produced and regulated by central and peripheral biological factors, and oxidative stress (OS) can aggravate it. However, previous studies only showed that impulsive behavior was related to the level of the peripheral OS. Therefore, this study aims to clarify the relationship between OS and impulsive behavior in the brain and peripheral blood., Methods: We recruited 64 Chinese men. We measured superoxide dismutase (SOD) (including copper, zinc and manganese) and nitric oxide synthase (NOS) (including total, inducible and constitutive) in cerebrospinal fluid (CSF) and plasma. The Barratt Impulsiveness Scale version 11 (BIS-11) was used to evaluate impulsive behavior. The relationship between OS and impulsive behavior was evaluated by partial correlation analysis and stepwise multiple regression analysis., Results: Partial correlation analysis showed that the ratio of total NOS-to-MnSOD and iNOS-to-MnSOD in CSF were negatively correlated with the BIS-11 motor scores (r = -0.431, p = -0.001; r = -0.434, p = -0.001). Stepwise multiple regression analysis showed that the ratio of CSF iNOS-to-MnSOD was the most influential variable on the BIS-11 motor scores(β = -0.434, t = -3.433, 95 %CI(-0.374, -0.098), p = 0.001)., Conclusions and Relevance: The imbalance of central oxidation and antioxidation is related to impulsive behavior, which broadens our understanding of the correlation between impulsive behavior and OS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Therapeutic strategies that target disease-associated transcripts are being developed for a variety of neurodegenerative syndromes. Protein levels change as a function of their half-life, a property that critically influences the timing and application of therapeutics. In addition, both protein kinetics and concentration may play important roles in neurodegeneration; therefore, it is essential to understand in vivo protein kinetics, including half-life. Here, we applied a stable isotope-labeling technique in combination with mass spectrometric detection and determined the in vivo kinetics of superoxide dismutase 1 (SOD1), mutation of which causes amyotrophic lateral sclerosis. Application of this method to human SOD1-expressing rats demonstrated that SOD1 is a long-lived protein, with a similar half-life in both the cerebral spinal fluid (CSF) and the CNS. Additionally, in these animals, the half-life of SOD1 was longest in the CNS when compared with other tissues. Evaluation of this method in human subjects demonstrated successful incorporation of the isotope label in the CSF and confirmed that SOD1 is a long-lived protein in the CSF of healthy individuals. Together, the results of this study provide important insight into SOD1 kinetics and support application of this technique to the design and implementation of clinical trials that target long-lived CNS proteins.

Superoxide dismutase 1 (SOD1) aggregation is one of the pathological markers of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. The underlying molecular grounds of SOD1 pathologic aggregation remains obscure as mutations alone are not exclusively the cause for the formation of protein inclusions. Thus, other components in the cell environment likely play a key role in triggering SOD1 toxic aggregation in ALS. Recently, it was found that ALS patients present a specific altered metabolomic profile in the cerebrospinal fluid (CSF) where SOD1 is also present and potentially interacts with metabolites. Here we have investigated how some of these small molecules affect apoSOD1 structure and aggregation propensity. Our results show that as co-solvents, the tested small molecules do not affect apoSOD1 thermal stability but do influence its tertiary interactions and dynamics, as evidenced by combined biophysical analysis and proteolytic susceptibility. Moreover, these compounds influence apoSOD1 aggregation, decreasing nucleation time and promoting the formation of larger and less soluble aggregates, and in some cases polymeric assemblies apparently composed by spherical species resembling the soluble native protein. We conclude that some components of the ALS metabolome that shape the chemical environment in the CSF may influence apoSOD1 conformers and aggregation.

The mutated SOD1 protein appears to have a gene dose-dependent effect on the severity and progression of ALS. Lowering of SOD1 protein levels might reduce severity and progression of the disease. The antimalarial drug pyrimethamine (PYR) was identified to cause a dose-dependent reduction in SOD1 protein levels in human cells in vitro. To determine if there was a similar effect in humans, we performed a phase I pilot study in 16 ALS patients with SOD1 mutations, 18 weeks in duration. Blood samples were obtained during all visits. The actin normalized leukocyte SOD1 levels were analyzed using Western blot. SOD1 content in the cerebrospinal fluid (CSF) was determined by ELISA and the SOD1 enzymic activity by spectrophotometric analysis using KO2. Clinical assessment of disease severity was assessed using Appel ALS scale and ALSFRS-R. The leukocyte SOD1 levels showed a significant reduction (p > 0.0001) by the third study visit and this reduction was sustained throughout the remainder of the study. CSF also showed a decrease in SOD1 protein content and enzymic activity in the two patients so tested. Thus, PYR use may be associated with a reduction in SOD1 in ALS patients. The significance is uncertain and further detailed study is required.

Background: Therapies designed to decrease the level of SOD1 are currently in a clinical trial for patients with superoxide dismutase (SOD1)-linked familial amyotrophic lateral sclerosis (ALS)., Objective: To determine whether the SOD1 protein in cerebral spinal fluid (CSF) may be a pharmacodynamic marker for antisense oligonucleotide therapy and a disease marker for ALS., Design: Antisense oligonucleotides targeting human SOD1 were administered to rats expressing SOD1G93A. The human SOD1 protein levels were measured in the rats' brain and CSF samples. In human CSF samples, the following proteins were measured: SOD1, tau, phosphorylated tau, VILIP-1, and YKL-40., Participants: Ninety-three participants with ALS, 88 healthy controls, and 89 controls with a neurological disease (55 with dementia of the Alzheimer type, 19 with multiple sclerosis, and 15 with peripheral neuropathy)., Results: Antisense oligonucleotide-treated SOD1G93A rats had decreased human SOD1 messenger RNA levels (mean [SD] decrease of 69% [4%]) and decreased protein levels (mean [SD] decrease of 48% [14%]) in the brain. The rats' CSF samples showed a similar decrease in hSOD1 levels (mean [SD] decrease of 42% [14%]). In human CSF samples, the SOD1 levels varied a mean (SD) 7.1% (5.7%) after additional measurements, separated by months, were performed. The CSF SOD1 levels were higher in the participants with ALS (mean [SE] level, 172 [8] ng/mL; P<.05) and the controls with a neurological disease (mean [SE] level, 172 [6] ng/mL; P<.05) than in the healthy controls (mean [SE] level, 134 [4] ng/mL). Elevated CSF SOD1 levels did not correlate with disease characteristics in participants with ALS or controls with dementia of the Alzheimer type, but they did correlate with tau, phosphorylated tau, VILIP-1 and YKL-40 levels in controls with dementia of the Alzheimer type., Conclusions: SOD1 in CSF may be an excellent pharmacodynamic marker for SOD1-lowering therapies because antisense oligonucleotide therapy lowers protein levels in the rat brain and rat CSF samples and because SOD1 levels in CSF samples from humans are stable over time.

Purpose: Our previous study using proteomic analysis showed that superoxide dismutase 1 (SOD1) was significantly decreased in cerebrospinal fluid (CSF) of patients with epilepsy. However, the relevance of CSF-SOD1 alterations for the pathophysiology of epilepsy is currently unknown. The present study was intended to add to our understanding of this issue by measuring SOD1 levels in the CSF of patients with resistant epilepsy and non-resistant epilepsy., Methods: A total of 52 patients with epilepsy were recruited. 29 were non-resistant, 23 drug-resistant. 20 individuals with no evidence of any neurological diseases were used as control. The concentration of CSF and serum SOD1 was measured by enzyme-linked immunosorbent assay., Results: The concentration of CSF-SOD1 was decreased in both the drug-resistant (0.13 ± 0.12 ng/ml) and the non-resistant epilepsy subgroups (0.29 ± 0.23 ng/ml) compared to the control group (0.40 ± 0.35 ng/ml). SOD1 was significantly lower in the drug-resistant than the non-resistant epilepsy subgroup (P<0.05)., Conclusion: SOD1 levels are decreased in the CSF of patients with epilepsy, especially of patients with intractable epilepsy. Low CSF-SOD1 levels may be a predictor of antiepileptic drug resistance in patients with epilepsy., (Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Several of the superoxide dismutase-1 (SOD1) mutations linked to amyotrophic lateral sclerosis (ALS) lead to synthesis of structurally defective molecules, suggesting that any cytotoxic conformational species common for all mutations should be misfolded. SOD1 can be secreted and evidence from ALS model systems suggests that extracellular SOD1 may be involved in cytotoxicity. Three ELISAs specifically reacting with different sequence segments in misfolded SOD1 species were used for analysis of CSF from 38 neurological controls and from 96 ALS patients, 57 of whom were sporadic cases and 39 familial, including 22 patients carrying SOD1 mutations. Misfolded SOD1 was found in all samples. There were, however, no significant differences between patients with and without mutations, and between all the ALS patients and the controls. The estimated concentration of misfolded SOD1 in the interstitium of the CNS is a 1000 times lower than that required for appreciable cytotoxicity in model systems. The results argue against a direct cytotoxic role of extracellular misfolded SOD1 in ALS. Misfolded SOD1 in CSF cannot be used as a biomarker of ALS in patients with and without mutations in the enzyme., (© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.)

This study aimed to clarify the kinetics of copper-zinc (CuZn) and manganese (Mn) superoxide dismutase (SOD) activity in acute ischemic stroke victims. Using the nitrite method, we investigated sequential changes in CuZn and Mn SOD activity in the cerebrospinal fluid (CSF) of 8 patients with acute ischemic stroke. SOD activity in each patient was measured at 36 hours and 3, 7, 14, and 28 days after stroke. CuZn SOD activity in CSF peaked 3 days after stroke, with values gradually decreasing after 7 days. In contrast, Mn SOD activity remained significantly lower in the stroke group than in controls throughout the study. These findings may reflect differences between the 2 isoenzymes in terms of the distribution, role, and method of synthesis in brain tissue., (Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Proteomic analysis of cerebrospinal fluid (CSF) from patients with temporal lobe epilepsy (TLE) and controls was carried out using two-dimensional gel electrophoresis followed by liquid chromatography electrospray ionization tandem mass spectrometry. Five protein spots showed significant differential expression (p<0.05): vitamin D-binding protein (DBP) was elevated in the CSF of TLE patients whereas cathepsin D, apolipoprotein J, Fam3c, and superoxide dismutase 1 (SOD1) were decreased in the CSF of TLE patients. Additional six protein spots presented only in the CSF of epilepsy patients were identified as tetranectin (TN), talin-2, apolipoprotein E, immunoglobulin lambda light chain (IGL@), immunoglobulin kappa variable light chain 1-5 (IGKV1-5), and procollagen C-endopeptidase enhancer 1 (PCOLCE). Expression of DBP, SOD1 and talin-2 was validated by western blot. Our results may provide better understanding of the pathophysiologic mechanisms underlying epileptogenesis and possible epilepsy biomarkers.

HIV-associated cognitive neurological disorders (HAND) prevail in the antiretroviral therapy era. Proteomics analysis of CSF revealed expression of Cu/Zn superoxide dismutase (Cu/Zn SOD) in Hispanic women with cognitive impairment (CI). We tested the hypothesis that there is reduced capacity of antioxidant enzymes in CI by measures of expression and activity of Cu/Zn SOD, catalase, and Se-glutathione peroxidase in HAND. Our results showed that the function of these antioxidants was decreased in the CSF and monocytes of women with CI. These findings have important implications regarding their possible contribution to oxidative stress and in the diagnosis and therapy for HAND.

The understanding of oxidative damage in different neurodegenerative diseases could enhance therapeutic strategies. Our objective was to quantify lipoperoxidation and other oxidative products as well as the activity of antioxidant enzymes and cofactors in cerebrospinal fluid (CSF) samples. We recorded data from all new patients with a diagnosis of either one of the four most frequent neurodegenerative diseases: Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD) and lateral amyotrophic sclerosis (ALS). The sum of nitrites and nitrates as end products of nitric oxide (NO) were increased in the four degenerative diseases and fluorescent lipoperoxidation products in three (excepting ALS). A decreased Cu/Zn-dependent superoxide dismutase (SOD) activity characterized the four diseases. A significantly decreased ferroxidase activity was found in PD, HD and AD, agreeing with findings of iron deposition in these entities, while free copper was found to be increased in CSF and appeared to be a good biomarker of PD.

Currently the best studied mechanism for amyotrophic lateral sclerosis (ALS) is the one caused by mutations in the gene for cytosolic Cu/Zn-binding superoxide dismutase (SOD1). Mutant SOD1 protein causes motor neuron degeneration due to the gain of a novel toxic function. To evaluate the relevance of SOD1 levels in cerebrospinal fluid (CSF) in ALS patients, the SOD1 concentration was immunoassayed in the CSF of 11 patients with ALS and 19 neurological controls. The mean level of SOD1 in CSF from all samples was 45.5+/-11.3 ng/ml. There was no statistically significant difference between the levels of SOD1 in CSF of ALS patients and neurological control subjects. Here we show that the SOD1 concentration in the CSF is significantly higher in male ALS patients (54.0+/-9.0 ng/ml) compared to female ALS patients (38.1+/-6.4 ng/ml) (p=0.007). This gender difference is not observed in the CSF of neurological controls. This is the first report of a potential gender difference in levels of SOD1 in CSF of ALS patients. Further investigation of larger sample groups is needed to determine whether it is relevant to gender related differences in disease incidence.

The activity of SOD and CAT was measured in controls and 5 h after 5, 10 and 15 min of ischemia, as well as 1 or 2 days after 10 min of ischemia in the hippocampus and in the CSF. A significant increase in total SOD activity 5 h after ischemia was caused mainly by increased CuZn-SOD activity. The highest values were measured 5 h after 5 min ischemia (by 160%) and smallest if 15 min (by 40%) of ischemia was used. In comparison to the hippocampus, the activity of SOD in CSF increased equally after all intervals of ischemia. Activities of total SOD and CuZn-SOD after 10 min of ischemia in the hippocampus were significantly increased only after 5 and 24 h of reperfusion but in CSF they were increased after all examined intervals of reperfusion. The activity of CAT was significantly increased in the hippocampus after 5 (by 260%), 10 and 15 min (by 100%) of ischemia. CAT activity in CSF was increased equally after all intervals of ischemia (by 200%). Ischemic attack causes a rapid response in hippocampal tissue as well as in the CSF, represented by an increase in the activity of endogenous antioxidant enzymes SOD and CAT.

For acute posttraumatic period of heavy combined cranium-facial trauma (CFT) considerable activation of peroxide lipids oxidation in the liquor is typical beginning from the 1st day of posttraumatic period on the background of speedy and drastic depletion of fermentative and low-molecular antioxidant liquor system (in spite of introduction of antioxidants particularly a-tocopherol acetate). Non-adequate functioning of the system of antioxidant defense on the background of free radical activity splash can be considered as breakdown of the process of adaptive reaction forming. It leads to weighting the course of posttraumatic period of heavy combined cranium-facial trauma and its outcome as a whole.

To improve protein delivery to the CNS following intracerebroventricular administration, we compared the distribution of a human Cu/Zn superoxide dismutase:tetanus toxin fragment C fusion protein (SOD1:TTC) in mouse brain and spinal cord with that of tetanus toxin fragment C (TTC) or human SOD1 (hSOD1) alone, following continuous infusion into the lateral ventricle. Mice infused with TTC or SOD1:TTC showed intense anti-TTC or anti-hSOD1 labeling, respectively, throughout the CNS. In contrast, animals treated with hSOD1 revealed moderate staining in periventricular tissues. In spinal cord sections from animals infused with SOD1:TTC, the fusion protein was found in neuron nuclear antigen-positive (NeuN+) neurons and not glial fibrillary acidic protein-positive (GFAP+) astrocytes. The percentage of NeuN+ ventral horn cells that were co-labeled with hSOD1 antibody was greater in mice treated with SOD1:TTC (cervical cord = 73 +/- 8.5%; lumbar cord = 62 +/- 7.7%) than in mice treated with hSOD1 alone (cervical cord = 15 +/- 3.9%; lumbar cord = 27 +/-4.7%). Enzyme-linked immunosorbent assay for hSOD1 further demonstrated that SOD1:TTC-infused mice had higher levels of immunoreactive hSOD1 in CNS tissue extracts than hSOD1-infused mice. Following 24 h of drug washout, tissue extracts from SOD1:TTC-treated mice still contained substantial amounts of hSOD1, while extracts from hSOD1-treated mice lacked detectable hSOD1. Immunoprecipitation of SOD1:TTC from these extracts using anti-TTC antibody revealed that the recovered fusion protein was structurally intact and enzymatically active. These results indicate that TTC may serve as a useful prototype for development as a non-viral vehicle for improving delivery of therapeutic proteins to the CNS.

Objectives: Experimental studies provide evidence that oxidative damage plays a role in the development of vasospasm after aneurysmal subarachnoid hemorrhage (SAH) but data from human studies is still limited. The purpose of this study was to investigate the time course of cerebrospinal fluid (CSF) superoxide dismutase (SOD) and serum malondialdehyde (MDA) changes in patients with aneurysmal SAH., Methods: SOD in CSF and MDA in the serum were detected on days 1-3, 5 and 7 after aneurysmal SAH in 21 patients, and the results were compared with 15 patients with hydrocephalus. The results were also compared with those of clinical parameters including the patient's outcome at 6 months., Results: The mean CSF SOD levels were lower and serum MDA levels were higher than the controls. Patients with a high amount of blood within the cisterns had a trend to decreased SOD while increasing MDA levels., Conclusion: These preliminary results suggest that the levels of antioxidants are decreased after the onset of SAH in the early period, possibly because of increased oxidative stress. Reactive oxygen-mediated oxidative damage may play an important role in inflammation after SAH.

Hydroxyl radical, ascorbate free radical, superoxide dismutase (SOD) activities, Cu,Zn-SOD protein, Mn-SOD protein, 8-hydroxy-2' -deoxyguanosine (8-OHdG) and metals were compared in red blood cells (RBC), plasma and/or cerebrospinal fluid (CSF) between patients with sporadic amyotrophic lateral sclerosis (SALS), familial ALS (FALS) showing the Leu126Ser mutation in the Cu, Zn-SOD gene and controls. In patients with FALS or SALS, concentrations of hydroxyl radical in blood and ascorbate free radical and 8-OHdG in CSF were higher than control group values, while SOD activities in RBC and CSF were lower. In contrast, Cu, Zn-SOD protein concentrations in RBC were low only in FALS patients. Concentrations of Cu in CSF of SALS patients were higher than in controls. Thus, the pathogenesis of increased oxidative stress differs between SALS patients and FALS patients with a mutant Leu126Ser SOD1 gene.

Background: The antioxidant status of the tissue affected by ischemia-reperfusion is of great importance for the primary endogenous defense against the free-radical-induced injury., Objective: In this study, we aimed to evaluate the relationship between the activities of antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT)] in cerebrospinal fluid (CSF) and severity of hypoxic-ischemic encephalopathy (HIE) in newborns., Methods: Thirty full-term asphyxiated infants (gestational age >37 weeks) and 11 full-term infants (none of whom showed any signs of asphyxia) were included in this study. Activities of SOD, GPX, and CAT in CSF were measured within the first 72 h of life in infants with HIE and controls., Results: Activity of SOD in CSF was significantly higher in infants with HIE compared with controls (p<0.05). GPX and CAT activities were higher in infants with HIE than they were in controls; however, the differences were not statistically significant (p > 0.05). The activities of GPX and CAT were significantly increased in severe HIE as compared with mild HIE and controls (p < 0.05)., Conclusion: Both the duration of the hypoxic-ischemic insult and the severity of HIE modulate elevations of enzymatic activity as an adaptive response to excessive free radical production in CSF in newborn infants with HIE. The activities of antioxidant enzyme alterations in CSF correspond highly to the severity of HIE, and these patterns may be useful for diagnostic and prognostic purposes., (Copyright (c) 2005 S. Karger AG, Basel.)

To determine whether or not the occurrence of sporadic amyotrophic lateral sclerosis (sALS) is associated with both excess nitric oxide (NO) metabolites and decreased protective superoxide dismutase (SOD) activity in the cerebrospinal fluid (CSF), we measured nitrate concentration and SOD activity in the CSF of sALS patients and in age- and gender-matched controls. We found stable NO metabolite levels to be significantly higher and SOD activity lower in the CSF of sALS patients. In addition, SOD showed a negative correlation with motor neuron axonal damage expressed as the amplitude of motor action potentials in upper limbs. Our results provide new evidence in vivo suggesting that NO products and SOD activity play a role in oxidant/ antioxidant imbalance in sporadic ALS.

Background and Purpose: Although activation of the N-methyl-D-aspartate (NMDA) receptor is thought to contribute to altered cerebrovascular regulation after traumatic brain injury, the effects of such injury on the vascular response to NMDA itself has been less well appreciated. The newly described opioid nociceptin/orphanin FQ (NOC/oFQ) elicits pial artery dilation, at least in part, in a prostaglandin-dependent manner and is released into cerebrospinal fluid after fluid percussion brain injury (FPI). Generation of superoxide anion (O(2)(-)) occurs after FPI, and a byproduct of cyclooxygenase metabolism is the generation of O(2)(-). This study was designed to determine whether NOC/oFQ generates O(2)(-), which in turn could link NOC/oFQ release to impaired NMDA-induced pial artery dilation after FPI., Methods: Injury of moderate severity (1.9 to 2.1 atm) was produced by the lateral FPI technique in anesthetized newborn pigs equipped with a closed cranial window. Superoxide dismutase-inhibitable nitroblue tetrazolium (NBT) reduction was determined as an index of O(2)(-) generation., Results: Under non-brain injury conditions, topical NOC/oFQ (10(-)(10) mol/L, the concentration present in cerebrospinal fluid after FPI) increased superoxide dismutase-inhibitable NBT reduction from 1+/-1 to 20+/-3 pmol/mm(2) but had no effect itself on pial artery diameter. Indomethacin (5 mg/kg IV) blunted such NBT reduction (1+/-1 to 6+/-2 pmol/mm(2)), whereas the NOC/oFQ receptor antagonist [F/G] NOC/oFQ (1-13) NH(2) (10(-)(6) mol/L) blocked NBT reduction. [F/G] NOC/oFQ (1-13) NH(2) and indomethacin also blunted the NBT reduction observed after FPI (1+/-1 to 15+/-1 versus 1+/-1 to 4+/-1 versus 1+/-1 to 4+/-1 pmol/mm(2) for sham, NOC/oFQ antagonist, and indomethacin-treated animals, respectively). NMDA (10(-)(8) and 10(-)(6) mol/L)-induced pial artery dilation was reversed to vasoconstriction after FPI, and [F/G] NOC/oFQ (1-13) NH(2) attenuated such vasoconstriction (sham 9+/-1% and 16+/-1% versus FPI -7+/-1% and -12+/-1% versus FPI-[F/G] NOC/oFQ (1-13) NH(2)-pretreated animals -2+/-1% and -3+/-1%). Indomethacin and the free radical scavengers polyethylene glycol superoxide dismutase and catalase also partially restored NMDA-induced vasodilation., Conclusions: These data show that NOC/oFQ, in concentrations present in cerebrospinal fluid after FPI, increased O(2)(-) production in a cyclooxygenase-dependent manner and contributes to such production after FPI. These data show that NOC/oFQ contributes to impaired NMDA-induced pial artery dilation after FPI. Therefore, these data suggest that cyclooxygenase-dependent O(2)(-) generation links NOC/oFQ release to impaired NMDA-induced cerebrovasodilation after brain injury.

Peroxynitrite can nitrate tyrosine residues of proteins. We examined nitrotyrosine-containing proteins in cerebrospinal fluid of 66 patients with neurogenic disease by immunoblot analysis. Nitrated tyrosine residue-containing protein was observed in the cerebrospinal fluid and was concluded to be manganese superoxide dismutase (Mn-SOD). The nitrated Mn-SOD level was strikingly elevated in amyotrophic lateral sclerosis patients and was slightly increased in Alzheimer's and Parkinson's disease patients, whereas an elevated Mn-SOD level was observed only in progressive supranuclear palsy group.

Acetylcholinesterase (AChE), choline, monoamine and its metabolite, amino acid and superoxide dismutase (SOD) levels were measured in cerebrospinal fluid (CSF) in patients with cerebrovascular diseases. Patients were classified into the following four groups; controls: normal subjects without neurological disease, group A: cerebral hemorrhage, group B: cerebral infarction, group C: patients with mental impairment, including those in groups A and B, and a low score on Hasegawa's Dementia Rating Scale. CSF AChE level of groups A, B and C was decreased significantly, while choline concentration from patients showed a increase compared with that of control cases. CSF alanine concentration showed a tendency to increase, while glycine and glutamate tended to decrease. CSF epinephrine, norepinephrine or 3-methoxy-4-hydroxyphenylethylen glycol concentrations of groups A, B and C did not exhibit a significant difference from that in control cases. Some cases with cerebrovascular diseases showed low concentrations of both CSF 5-hydroxyindole acetic acid and homovanillic acid. However, dihydroxyphenyl acetic acid concentration was higher than in control cases. The CSF SOD level was not significantly from that in control cases. The changes in neurochemical substances in the CSF support their use as markers of cerebrovascular disease-related change.

The study was undertaken to evaluate the role of free oxygen radicals in asphyxiated neonates. Thirty term neonates appropriate for gestational age and with severe birth asphyxia (Apgar score of 3 or less at 1 minute of life) formed the study subjects. The levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), creatine phosphokinase (CPK) and lipid peroxidase (LPO) in the CSF of these neonates were estimated between 12 and 48 hrs of life. Enzyme estimation was performed by standard methods and the results were analysed statistically using Multivariate Logistic Regression analysis and non parametric tests namely Kruskal Wallis test and Wilcoxon's rank sum test. Out of the thirty babies, 14 were observed to be neurologically normal, 9 had significant morbidity and 7 died. The SOD levels ranged from 12.4 to 140 units/ml, GPx from 128 to 1933 nmol/min/dl, CPK from 2 to 2098 IU/dl and LPO from 5.4 to 30.8 umol/hr/dl. The SOD and GPx levels had an inverse relationship whereas rise in LPO and CPK levels were directly proportional to the extent of neurological damage and ultimate clinical outcome. CPK levels higher than 140 IU/ml were lethal and associated with 100% mortality whereas all normal neonates had CPK below 37 IU/ml. The levels of antioxidant enzymes can reliably and significantly predict mortality and morbidity whereas level of an enzyme cannot confidently confer normalcy. Hence antioxidant enzyme levels with a cut off value can be a useful marker and serve as a prognostic indicator in times to come.

Data on superoxide dismutase (SOD) activity in the cerebrospinal fluid (CSF) of patients suffering from dementia (n=32) as compared with a control group (n=58), a Parkinson disease (PD) patient group (n=12), and a group of individuals suffering from epilepsy (n=13) are presented. SOD activity was determined by electron spin resonance spectrometry using the spin trap method. No significant correlation was found between CSF SOD activity and age in the control group. In addition, CSF SOD activity was not gender dependent. One-way analysis of variance showed a highly significant between-groups effect for the CSF SOD activity and specific CSF SOD activity of the four major groups (p=0.0008). Post hoc comparison (Fisher PLSD test) revealed significant differences between the control group and the total dementia group (p < 0.001), between the dementia group and the epilepsy group (p < 0.01), and between the dementia group and the PD group (p < 0.05). The CSF of patients with PD or epilepsy showed a similar SOD activity as the CSF of control patients. In addition, CSF SOD activity levels were significantly lower in the total dementia group (p=0.002) and in the group with dementia of the Alzheimer type (DAT) (p=0.001) than in the dementia age-matched control group. No significant difference was found for CSF SOD activity levels between the control group and the non-DAT dementia group. This result corresponded with a reduction of CSF SOD activity in the total dementia group, DAT subgroup, and non-DAT subgroup of 37, 43, and 22%, respectively. No significant correlation between the Mini-Mental State Examination score and CSF SOD activity was found in DAT. The lowered CSF SOD activity in Alzheimer disease, as demonstrated here, may reflect impaired radical defense mechanisms and may have possible pathophysiological significance.

It has been recognised that the level of superoxide dismutase (SOD) significantly increases in CSF as the result of cerebral ischaemic damage. The aim of this study was to correlate the CSF levels of SOD enzymatic activity to the patterns of subarachnoid haemorrhage with regards to ischaemic complications due to vasospasm. A series of 78 patients operated on for intracranial aneurysms was studied; all patients were monitored with serial TCD measurements every second day after SAH. CSF samples were obtained at surgery by cisternal puncture of the subarachnoid cistern nearest to the aneurysm. SOD activity was assayed spectrophotometrically. Mean cisternal CSF level of SOD in 12 control cases (12.99 +/- 2.33 U/ml) is significantly higher (p < 0.01) than in 26 patients operated on between day 1 and 3 from last SAH episode (4.44 +/- 0.7 U/ml) and in 40 patients treated by delayed surgery (7.64 +/- 0.92 U/ml). In 13 patients presenting neurological deterioration related to arterial vasospasm mean cisternal SOD level was 12.23 +/- 1.86 U/ml; in 27 cases without vasospasm mean level was 5.43 +/- 0.7 U/ml (p < 001). The present results suggest that (a) cisternal CSF levels of SOD significantly decreases after SAH, probably in relation to an impaired synthesis in the brain compartment and that (b) a substantial elevation of SOD levels is evident in patients suffering ischaemic complications vasospasm-related. Biochemical events in the brain compartment could influence the expression and release of anti-oxidant enzymes in CSF after SAH.

We investigated superoxide dismutase (SOD) activity in human cerebrospinal fluid (CSF) as an index of the aging process in the central nervous system (CNS). The subjects were 61 individuals aged 21-77 years, comprising 24 men and 37 women without organic disorders of the nervous system. SOD activity in CSF was measured by the nitrite method modified by Oyanagui. The results showed that SOD activity in CSF gradually increased with age and that the values of SOD activity after the fifth decade were significantly higher than those in the third and fourth decades. It might suggest that the productivity of SOD in the CNS gradually increased with age due to stimulation of various types of oxidative stress which accumulated in vivo especially after the fifth decade.

In the pathophysiology of lumbosacral radiculopathy, inflammation of the nerve root is of critical importance. Additionally, free radicals have been shown to be associated with some inflammatory process. This study was designed to investigate whether free radicals participate in the pathophysiology of nerve root involvement. We measured superoxide dismutase (SOD) activity in cerebrospinal fluid (CSF) of 31 patients with unilateral lumbosacral radiculopathy caused by a herniated disc using electron spin resonance (ESR) spectrometry. Then SOD activity was compared with the type of nerve root compression as seen on preoperative myelography. SOD activity in the normal control group was 7U/ml, while that in the hernia group remarkably decreased. The concentration gradient of SOD activity was different between central herniation and centrolateral herniation. Our findings indicate that free radicals are generated after nerve root compression. Under severe deficiency of SOD activity in CSF, serum SOD penetrates into CSF after further compression. In addition, SOD in CSF may play an important role in protecting against nerve root involvement.

We examined the mechanism of increase of manganese superoxide dismutase (Mn SOD) in the cerebrospinal fluid (CSF) in bacterial meningitis (BM). The elevated levels of Mn SOD in the CSF in BM, measured with an enzyme immunoassay method, were more prominent than those in aseptic meningitis (AM) and encephalitis (EN). In AM and EN Mn SOD levels well correlated with levels of neuron-specific enolase and S-100b protein, which are markers of damages to nervous tissues, but did not with any of them in BM. CSF concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) were higher in BM than in AM and EN. From the serial measurements in BM, the peak values of these cytokines chronologically preceded or corresponded to those of Mn SOD. Immunohistochemically, a large number of the glial cells were stained for Mn SOD in the cerebral cortex from a patient with BM. By contrast, in the normal cerebral cortex, the glial cells were negative for Mn SOD staining. These results suggest that the marked increase of Mn SOD in the CSF in BM may be related to the increase of such cytokines as TNF-alpha and IL-1 alpha and that these cytokines may play a role in the induction of Mn SOD in nervous tissues.

Cu, Zn superoxide dismutase (SOD) levels in the serum, cerebrospinal fluid (CSF) and skin fibroblasts of patients with dementia of the Alzheimer type (DAT) were estimated using enzyme immunoassay. The SOD mRNA level in the skin fibroblasts was also determined by the Northern blot analysis. As compared with the age-matched control groups of neurological patients without dementia, the AD group consisting of patients with DAT at ages under 65 years of age as well as the SDAT group of patients with DAT at ages over 65 years of age showed no significant changes in serum or CSF SOD levels. However, the skin fibroblast SOD- and SOD mRNA levels, which were correlate each other, were significantly higher in the AD group (p < 0.05), while lower in the SDAT group (p < 0.05). These results suggest that the determination of the SOD level of skin fibroblast may be useful for diagnosis of DAT and that the abnormality of SOD may play an important role in developing DAT.

We measured cerebrospinal fluid (CSF) levels of Cu/Zn superoxide dismutase (Cu/Zn SOD) and Mn superoxide dismutase (Mn SOD) using enzyme immunoassays in 196 neurological patients and 44 controls. The mean Cu/Zn SOD level was 55.8 +/- 27.6 (SD) ng/ml and the Mn SOD, 8.0 +/- 2.5 ng/ml in the controls. Cu/Zn SOD or Mn SOD levels showed neither age-nor sex-related differences in the controls. Both SODs were markedly elevated in cerebrovascular diseases, bacterial meningitis and encephalitis. Mn SOD alone was significantly elevated in neurodegenerative diseases. We compared SODs with CSF levels of neuron-specific enolase (NSE) and S-100b protein (S-100b) in cerebral infarction and bacterial meningitis. Both SODs were correlated with NSE and S-100b in patients with cerebral infarction, but not in those with bacterial meningitis. This means that elevations of SODs in CSF may not only be due to leakage from damaged nervous tissues, but also to the induction of SOD in lesions. We conclude that the mean SOD levels were elevated in various neurological diseases, and their varied magnitudes may be associated with the underlying diseases.

We measured cerebrospinal fluid (CSF) levels of manganese superoxide dismutase (Mn SOD) using an enzyme immunoassay method in 19 patients with bacterial meningitis (BM), 33 with aseptic meningitis (AM) and 13 with encephalitis (EN), and examined the significance of their elevations, especially in BM. 1) In BM, the Mn SOD levels were obviously high, ranging from 10.4 to 1179.2 ng/ml. The mean level of Mn SOD was 234.6 +/- 306.7 (SD) ng/ml and 18 patients showed abnormal levels of Mn SOD (more than 13.1 ng/ml). On the other hand, in the remaining 2 diseases, the elevation of SOD levels was not remarkable: the mean levels of Mn SOD in AM and EN were 20.6 +/- 11.6 ng/ml and 41.9 +/- 23.6 ng/ml, respectively. 2) In AM and EN, Mn SOD levels well correlated with NSE or S-100b levels which are the markers of nervous tissue damages. But there was no correlation between the Mn SOD levels in BM and these markers. 3) In BM, there was a positive relationship between Mn SOD and total protein levels, but the disease days showing peak levels were different between them. In addition, Mn SOD levels showed no correlation with cell counts in CSF. 4) In BM, CSF levels of TNF-alpha and IL-1 alpha were remarkably high, whereas in AM and EN, the increases of these cytokines were not marked. And these cytokines in BM showed the peak values in the disease day before or when Mn SOD reached the peak levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Superoxide dismutase (SOD), neuron specific enolase (NSE) and lactic dehydrogenase (LDH) were measured in the serum and cerebrospinal fluid (CSF) of ischemic cerebrovascular patients, other neurological patients and in age-matched healthy controls (serum only). The levels of SOD in the CSF or serum of the ischemic patients in the first 24 hrs after stroke were similar to the control groups. However, SOD levels in the ischemic patients increased after two days, reaching their peak values after one week (2-3 fold of the initial values). NSE showed a similar kinetics while LDH showed no change. These results suggest that oxygen radicals are formed in the ischemic patients and the increased synthesis of SOD may protect the patients from the potential damage of such radicals.

To evaluate significance of superoxide dismutase in neurological diseases, we measured cerebrospinal fluid (CSF) levels of copper-zinc superoxide dismutase (Cu/Zn SOD) and manganese superoxide dismutase (Mn SOD) using enzyme immunoassay methods in 181 neurological patients and 43 controls. The mean level of Cu/Zn SOD in CSF of controls was 54.4 +/- 28.7 ng/ml, and that of Mn SOD 8.1 +/- 2.5 ng/ml, although other methods have reported that Mn SOD is undetectable in CSF. Cu/Zn SOD or Mn SOD showed no statistical difference in age or sex of the controls. The elevation of both SOD levels was marked in acute diseases such as cerebrovascular diseases (CVD), bacterial meningitis and encephalitis, but mild in aseptic meningitis. The elevation of Cu/Zn SOD level was more prominent than that of Mn SOD in CVD, whereas vice versa in bacterial meningitis and encephalitis. In neurodegenerative diseases and cervical spondylosis, only Mn SOD level was significantly elevated. To examine the source of CSF SOD, we compared it with CSF levels of neuron-specific enolase (NSE) and S-100b protein (S-100b) in cerebral infarction and bacterial meningitis. Both SOD levels were correlated with NSE and S-100b levels in patients with cerebral infarction, but in bacterial meningitis no significant relationship was found among SOD levels, NSE and S-100b levels. This means that elevations of SODs in CSF may be due to not only damage of the nervous tissues but also the other mechanisms, as induction of SOD in the lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral vasospasm may result from lipid peroxidation induced by oxyhemoglobin in the subarachnoid space after subarachnoid hemorrhage. To test this theory, vasospasm was induced in monkeys by intrathecal injections of oxyhemoglobin or supernatant fluid from autologous blood incubated in vitro. Concentration of malondialdehyde (MDA), a product of lipid peroxidation, was elevated in cerebrospinal fluid (CSF) in association with vasospasm caused by oxyhemoglobin and supernatant fluid. Intrathecal injections of methemoglobin or bilirubin did not cause vasospasm or increased CSF MDA. Activity of glutathione peroxidase in CSF increased significantly after injection of oxyhemoglobin and methemoglobin. There were no significant changes in CSF superoxide dismutase activity although there was a trend towards higher activities in animals treated with oxyhemoglobin, methemoglobin, bilirubin, and supernatant fluid. These results show oxyhemoglobin-induced vasospasm is associated with MDA and lipid peroxidation in the subarachnoid space. Furthermore, detection of peroxidation products after injection of oxyhemoglobin in the absence of erythrocyte membranes indicates that oxyhemoglobin may directly damage cerebral arteries and brain by inducing lipid peroxidation in these structures. Depletion of free-radical scavenging enzymes in CSF did not seem necessary for development of vasospasm. In fact, there was a tendency for vasospasm to elevate enzyme activities, as if production of scavengers was induced by excess free radicals in the subarachnoid space.

Background and Purpose: Evaluation of biochemical patterns in cerebrospinal fluid may add diagnostic and prognostic information. We tested to determine whether the concentration of superoxide dismutase in cerebrospinal fluid is a marker of brain tissue damage in acute ischemic stroke., Methods: We investigated 36 acute ischemic stroke patients for cerebrospinal fluid activity of the enzyme superoxide dismutase on two occasions shortly after symptom onset (average, day 1 and day 4)., Results: In 75% of the patients, the first of two lumbar punctures revealed the maximal superoxide dismutase value. The amount in the cerebrospinal fluid was significantly correlated with the size of infarction on computed tomographic scan (p less than 0.001 by analysis of variance) and to functional impairment and stroke-related mortality during initial hospital stay (p less than 0.002). The correlation of initial superoxide dismutase concentration with the need for long-term institutional care and mortality at 3 months after the stroke was also significant (p less than 0.03)., Conclusions: We conclude that superoxide dismutase in cerebrospinal fluid is a marker of an acute brain lesion and has some value as a prognostic predictor. This small enzyme leaks rapidly from ischemically injured cells.

Activity of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase as well as content of diene conjugates and malonic dialdehyde were studied in blood serum and cerebrospinal fluid of patients with transitory ischemia, small ischemic insult, ischemic insult of middle severity and with severe ischemic insult without lethality within 1-2, 7-8 and 14-15 days of diseases. Content of lipid peroxidation products and activity of antioxidant enzymes were decreased in the biological fluids studied in all the forms of brain circulation impairments within early periods of pathology. These patterns tend to normalization within 14-15 days. The rate of biochemical alterations corresponded highly to severity of impairments developed and these patterns may be used for diagnostic and prognostic purposes.

Superoxide dismutase (SOD) activity in CSF of patients was determined by electron spin resonance spectrometry using the spin trap method. Variation in SOD activity was found among patients. SOD activity in CSF of subjects increased with age and this was identified as Cu,Zn-SOD activity by electrophoresis. In addition, animal experiments showed that SOD activities were higher in mitochondrial and cytosol fractions of aged rats than in those of adult rats. This finding on aged rat brain validates the increase of SOD activity in aged human CSF.

We determined the concentration of copper zinc superoxide dismutase (CuZnSOD) in cerebrospinal fluid (CSF) and plasma of 36 persons without neurological illness or with various central and peripheral nervous system disorders not supposed to generate abnormal radical formation. The CuZnSOD concentration in CSF was significantly higher compared with plasma, suggesting the presence of a high oxygen-radical load on the central nervous system. Our data may be considered to reflect normal values.

The activity of the superoxide dismutase was measured by the polarographic method of catalytic currents in the cerebrospinal fluid of patients with age-related neurologic degenerative diseases, namely, amyotrophic lateral sclerosis and Alzheimer's disease, and of a reference group of normal subjects. The superoxide dismutase activity was found to increase with age in reference subjects (r = 0.81) while no significant correlation was found in amyotrophic lateral sclerosis and Alzheimer's disease patients. The activity mean values were significantly lower (P less than 0.01) in patients with neurologic degenerative diseases than in the reference subjects. The changes of superoxide dismutase activity in the aging brain and in age-related neurologic degenerative diseases are discussed.

The neuronal ceroid-lipofuscinoses is a group of diseases characterized by a widespread accumulation in the body of pigments believed to be end-products of lipid-peroxidation damaged organelles. It was recently shown that cerebrospinal fluid from patients with infantile and juvenile neuronal ceroid-lipofuscinosis were less protective against superoxide radical-induced hydroxyl radical formation compared with controls. The content of superoxide dismutase isoenzymes in cerebrospinal fluid and in plasma from patients with different forms of neuronal ceroid-lipofuscinosis was analysed. No significant difference from controls could be demonstrated in samples from patients with juvenile neuronal ceroid-lipofuscinosis. The few samples from patients with infantile and late infantile neuronal ceroid-lipofuscinosis analysed all fell within the range defined by the controls.