Continuous lumbar drainage after aneurysmal subarachnoid hemorrhage decreased malondialdehyde in cerebrospinal fluid and improved outcome.

PURPOSE: The use of a continuous lumbar drain (LD) for the treatment of aneurysmal subarachnoid hemorrhage (aSAH), and malondialdehyde (MDA), a marker of oxidative stress, is correlated with clinical outcome. This study aimed to investigate the relationship between LD placement and MDA level after aSAH. METHODS: Patients with modified Fisher's grade III and IV aSAH who underwent early aneurysm obliteration were enrolled. Cerebrospinal fluid (CSF) was obtained on day 7 after aSAH in non-LD group. In LD group, the LD was inserted on day 3 after aSAH for continuous CSF drainage. The levels of intrathecal hemoglobin, total bilirubin, ferritin, and MDA were measured. RESULTS: There were 41 patients in non-LD group (age: 58.7 ± 13.7 years; female: 61.0%) and 48 patients in LD group (age: 58.3 ± 10.4 years; female: 79.2%). There were more favorable outcomes (Glasgow Outcome Scale ≥4) at 3 months after aSAH in LD group (p = 0.0042). The intrathecal hemoglobin, total bilirubin, ferritin, and MDA levels at day 7 after aSAH were all significantly lower in LD group. An older age (>60 years) (p = 0.0293), higher MDA level in the CSF (p = 0.0208), and delayed ischemic neurological deficit (p = 0.0451) were independent factors associated with unfavorable outcomes. LD placement was associated with a decreased intrathecal MDA level on day 7 after aSAH (p < 0.001). CONCLUSION: The intrathecal MDA level at day 7 after aSAH can be an effective outcome indicator in modified Fisher's grade III/IV aSAH. Continuous CSF drainage via a LD can decrease the intrathecal MDA level and improve the functional outcome.

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.

Piperine restores streptozotocin-induced cognitive impairments: Insights into oxidative balance in cerebrospinal fluid and hippocampus.

Piperine has been shown to have antioxidant activity and a cognitive-enhancing effect following long-term oral administration. In a comparative study of memantine, the current investigation threw light on the cognitive benefits of piperine. Lipid peroxidation and the ferric reducing antioxidant power (FRAP) of cerebrospinal fluid (CSF) and hippocampus in streptozotocin (STZ)-induced experimental dementia of the Alzheimer's type was measured. After reaching a criterion in a memory test, STZ-induced rats received piperine [2.5, 5, and 10mg/kg, intraperitoneally (i.p.)], vehicle, and memantine (10mg/kg, i.p.) for two weeks after the first STZ administration, or two weeks before and one week after, as a preventive approach. After the behavioral studies, samples were taken for biochemical and histological assays. An appropriate concentration of piperine (2.5mg/kg), on a daily basis, effectively increased the number of correct (non-repeated) arm entries and repressed reentry to a previously visited arm, in terms of reference errors as well as memantine (10mg/kg, i.p.), irrespective of the dose administered. The cognitive-enhancing effect induced by piperine at a relevant dose was simultaneous with CSF and hippocampal malonaldehyde decrement, and the redox balance was established to some extent by maintaining the FRAP levels of CSF near to those of the control. Similarly, the neuroprotective properties of piperine are in accordance with histopathological outcomes, which have shown an increased number of live cresyl violet (CV)-positive neurons in a dentate gyrus (DG) subregion. Therefore, the effects of piperine on the redox balance of CSF and hippocampal neurons may certainly contribute to the cognitive-enhancing activity of the drug.

Oxidative stress-related biomarkers in multiple sclerosis: a review.

AIM: To provide an up-to-date review of oxidative stress biomarkers in multiple sclerosis and thus identify candidate molecules with greatest promise as biomarkers of diagnosis, disease activity or prognosis. METHOD: A semi-systematic literature search using PubMed and other databases. RESULTS: Nitric oxide metabolites, superoxide dismutase, catalase, glutathione reductase, inducible nitric oxide synthase, protein carbonyl, 3-nitrotyrosine, isoprostanes, malondialdehyde and products of DNA oxidation have been identified across multiple studies as having promise as diagnostic, therapeutic or prognostic markers in MS. CONCLUSION: Heterogeneity of study design, particularly patient selection, limits comparability across studies. Further cohort studies are needed, and we would recommend promising markers be incorporated into future clinical trials to prospectively validate their potential.

Changes in levels of oxidative stress markers and some neuronal enzyme activities in cerebrospinal fluid of multiple sclerosis patients.

OBJECTIVES: The aim of the present study was to assess cerebrospinal fluid (CSF) levels of malondialdehyde (MDA), F2 isoprostanes (8-iso-PGF2α) and total antioxidant status (TAS) in relapsing-remitting (RR) and secondary progressive (SP) course of MS and neurological controls. These parameters were correlated with brain tissue damage parameters - neuron-specific enolase and 3´,5´-cAMP-phosphodiesterase (PDE) in CSF. METHODS: CSF samples were obtained from MS patients divided into two groups according to the disease severity (EDSS) - RR and SP course of MS. Control group composed of neurological diagnoses without demyelination and neurodegeneration. 8-iso-PGF2α and NSE levels in the CSF samples were determined using specific immunochemistry assays. MDA levels in the CSF were measured by HPLC method after reaction with thiobarbituric acid in acidic conditions. TAS and total PDE activity of CSF was determined spectrophotometrically. RESULTS: There were significant differences in CSF MDA levels between MS group and controls and also between RR and SP disease course. By contrast, CSF levels of 8-iso-PGF2α in MS group and both forms of MS were comparable to control values. In addition, the results show increased CSF levels of PDE in MS group and no changes of NSE in CSF between MS and control group. CONCLUSION: These findings point to a possibility of using the parameters of different specificity to lipid peroxidation for monitoring different stages (acute/progressive) of MS. This study support the idea, that combination of CSF markers is important for monitoring overall brain tissue pathology in MS.

Effects of WR1065 on 6-hydroxydopamine-induced motor imbalance: Possible involvement of oxidative stress and inflammatory cytokines.

Over production of reactive oxygen species (ROS) is postulated to be the main contributor in degeneration of nigrostriatal dopaminergic neurons. In this study we investigated the effects of WR1065, a free radical scavenger, on motor imbalance, oxidative stress parameters and inflammatory cytokines in CSF and brain of hemi-parkinsonian rats. Lesion of dopaminergic neurons was done by unilateral infusion of 6-hydroxydopamine into the central region of the substentia nigra pars compacta (SNc) to induce hemi-parkinsonism and motor imbalance in rats. WR1065 (20, 40 and 80µg/2µl/rat) was administered three days before 6-OHDA administration. After three weeks behavioral study was performed and then brain and CSF samples were collected to assess tumor necrosis factor (TNFα), interlukin (IL-1ß), reduced glutathione (GSH), and malondialdehyde (MDA). WR1065 pre-treatment in rats before receiving 6-OHDA, improved significantly motor impairment and caused reduction of MDA and inflammatory cytokines TNFα and IL-1ß levels, while GSH level significantly increased when compared with lesioned rats. Our study indicated that WR1065 could improve 6-OHDA-induced motor imbalance. Furthermore, it decreased lipid peroxidation and inflammatory cytokines and restored the level of GSH up to normal range. We suggest that WR1065 can be proposed as a potential neuroprotective agent in motor impairments of PD. However to prove this hypothesis more clinical trial studies should be done.

Lipid peroxidation in the pathogenesis of neuroborreliosis.

This study analyzed the onset of lipid peroxidation (LPO) in neuroborreliosis and the effects of ceftriaxone therapy on LPO. Twenty-two patients with early neuroborreliosis and 22 healthy subjects were studied. LPO in the cerebrospinal fluid (CSF), as well as the plasma and urine was estimated by the levels of reactive aldehydes: 4-hydroxynonenal (4-HNE), 4-hydroxyhexenal, malondialdehyde, and 4-oxononenal, F2-isoprostanes and A4/J4-neuroprostanes (NPs). The plasma level of 4-HNE-protein adducts arachidonic acid (AA), docosahexaenoic acid (DHA) and vitamin E was determined. Additionally, enzymatic activities of phospholipase A2 (PLA2), platelet-activating factor acetylhydrolase (PAF-AH) and glutathione peroxidase (GSH-Px) were determined. A decrease of AA, DHA levels and GSH-Px activity in plasma was associated with a significant increase of aldehydes in the CSF, plasma and urine. Similarly, the increase of F2-isoprostanes and NPs in the CSF and plasma was associated with the decreased activity of PLA2 and PAF-AH. Ceftriaxone therapy cured patients and reduced the levels of F2-isoprostanes, NPs and reactive aldehydes. However, the activities of PLA2 and PAF-AH increased. Pathophysiological association of neuroborreliosis with systemic LPO was revealed. Effective antibiotic therapy attenuated LPO. Biomarkers of LPO could be useful to monitor the onset of neuroborreliosis and show the effectiveness of pharmacotherapy.

Oxidant and antioxidant status in children with subacute sclerosing panencephalitis.

We analyzed serum alpha-tocopherol, beta-carotene, retinol, and ascorbic acid levels and malondialdehyde and reduced glutathione concentrations on erythrocyte and cerebrospinal fluid in 30 patients with subacute sclerosing panencephalitis to evaluate oxidant and antioxidant status. Serum alpha-tocopherol, beta-carotene, retinol, ascorbic acid levels, and erythrocyte and cerebrospinal fluid reduced glutathione concentrations were decreased; however, erythrocyte and cerebrospinal fluid malondialdehyde levels were increased in the patients. Cerebrospinal fluid malondialdehyde levels were different between clinical stages of the disease (P < .05). Higher cerebrospinal fluid malondialdehyde level was associated with the more severe clinical stage. A positive correlation was found between cerebrospinal fluid malondialdehyde level and clinical stages (r = 0.42; P < .05) and between erythrocyte malondialdehyde level and clinical stages (r = 0.40; P < .05). Our findings showed presence of oxidative damage in subacute sclerosing panencephalitis and that antioxidants were increased as defense mechanisms of the organism against oxidative damage.

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.

Changes in plasma and cerebrospinal fluid biomarkers in aged patients with early postoperative cognitive dysfunction following total hip-replacement surgery.

PURPOSE: We hypothesized that different patterns of biomarkers of brain injury and inflammation exist in aged patients with postoperative cognitive dysfunction (POCD) after total hip-replacement with spinal anesthesia. METHODS: Eighty-three patients older than 65 years undergoing elective total hip-replacement surgery were enrolled in this prospective observational study. The CSF levels of Tau, phosphorylated-tau (pTau), amyloidß1-42 (Aß1-42), Tau/Aß1-42, pTau/Aß1-42, BDNF, IL-6, and IL-1ß were measured preoperatively. Perioperative plasma levels of IL-1ß, IL-6, brain-derived neurotrophic factor (BDNF), C-reactive protein (CRP), and malonaldehyde (MDA) as well as neurocognitive tests were determined preoperatively and seven days postoperatively. RESULTS: Sixty-one patients completed both the CSF and blood samples collection and the neurocognitive tests. POCD occurred in 24.6 % of patients at seven days after surgery. Patients with POCD had significantly higher IL-1ß, Tau/Aß1-42, pTau/Aß1-42, and a lower level of Aß1-42 in CSF when compared with the Non-POCD group (P < 0.05). Furthermore, POCD patients displayed significantly higher plasma levels of MDA when compared with Non-POCD patients at seven days after surgery (P < 0.05). There was no difference in preoperative CSF levels of Tau, IL-6, and pTau as well as plasma levels of IL-1ß, IL-6, BDNF and CRP between POCD and Non-POCD groups (P > 0.05). CONCLUSION: The POCD patients were associated with higher postoperative plasma levels of MDA, and higher IL-1ß and lower Aß1-42 levels in preoperative CSF that might predispose the development of POCD in aged patients following total hip-replacement surgery with spinal anesthesia.

Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism.

Metabolomic and lipidomic analyses have been used for the profiling of neurodegenerative processes, both in targeted and untargeted approaches. In this work we have applied these techniques to the study of CSF samples of multiple sclerosis (MS) patients (n = 9), compared with samples of non-MS individuals (n = 9) using mass-spectrometry. We have used western-blot and analyzed cell culture to confirm pathogenic pathways suggested by mass-spectrometric measurements. The results of the untargeted approach of metabolomics and lipidomics suggest the existence of several metabolites and lipids discriminating both populations. Applying targeted lipidomic analyses focused to a pathogenic pathway in MS, oxidative stress, reveal that the lipid peroxidation marker 8-iso-prostaglandin F2α is increased in CSF from MS patients. Furthermore, as lipid peroxidation exerts its pathogenical effects through protein modification, we studied the incidence of protein lipoxidation, revealing specific increases in carboxymethylated, neuroketal and malondialdehyde-mediated protein modifications in proteins of CSF from MS patients, despite the absence of their precursors glyoxal and methylglyoxal. Finally, we report that the level of neuroketal-modified proteins correlated with a hitherto unknown increased amount of autoantibodies against lipid peroxidation-modified proteins in CSF, without compensation by signaling induced by lipid peroxidation via peroxisome proliferator-activated receptor γ (PPARγ). The results, despite the limitation of being obtained in a small population, strongly suggest that autoimmunity against in situ produced epitopes derived from lipid peroxidation can be a relevant pathogenic factor in MS.

Antioxidative enzymes activity and malondialdehyde concentration during mitoxantrone therapy in multiple sclerosis patients.

Mitoxantrone (MX) is approved for the treatment of aggressive relapsing-remitting, secondary-progressive and progressive-relapsing form of multiple sclerosis (MS). The mechanism of its action is multiaxial, however, it is not free from side effects. The causes of the side effects are still unknown and require further investigation. The aim of this study was to investigate the influence of MX therapy on enzymatic parameters of endogenous antioxidative status: manganese and copper/zinc superoxide dismutase (MnSOD, Cu/ZnSOD), catalase (CAT), glutathione peroxidase (GSH-Px) and lipid peroxidation marker--malondialdehyde (MDA) in blood serum and cerebrospinal fluid (CSF) in patients suffering from MS. After the MX therapy serum and the CSF MDA concentrations increased significantly. We reported that MnSOD activities decrease in serum and the CSF, while, surprisingly, the serum Cu/ZnSOD activity increases after the MX therapy. We also noted a marked decrease in CSF CAT and GSH-Px activity after the MX treatment. Our results strongly suggest the influence of MX therapy on oxidation/antioxidation status of serum and the CSF. These findings open up new opportunities for a better understanding of underlying physiopathological events in MS and provide a new insight into MX's mechanisms of action, especially its potent side effects.

Effect of high-dose phenobarbital on oxidative stress in perinatal asphyxia: an open label randomized controlled trial.

OBJECTIVE: To evaluate the effect of high dose phenobarbital on lipid peroxidation and antioxidant enzymes in perinatal asphyxia. DESIGN: Open label, Randomized controlled trial. SETTING: Neonatal intensive care unit of a tertiary care teaching hospital. PARTICIPANTS: 72 full term inborn neonates with severe birth asphyxia. METHODS: Neonates were randomized to Study (phenobarbital) group and Control group. The infants in the study group received phenobarbital infusion (40 mg/kg) within first two hours of life while babies in the control group did not receive any phenobarbital. Rest of the management in both the groups was as per the unit protocol for the management of hypoxic ischemic encephalopathy. A cerebrospinal fluid examination was done at 12 ± 2 hours of life to determine the levels of superoxide dismutase, glutathione peroxidise and malonyldialdehyde. 60 neonates were followed up at 1 month of age when a detailed neurological examination was done. RESULTS: Four neonates in the study group and six neonates in the control group died during the study. Two neonates in the study group were lost to follow up. The cerebrospinal fluid lipid peroxides and antioxidant enzymes were significantly lower in the phenobarbital group as compared to the control group. The neurological outcome at one month follow up was found to be comparable between the two groups. CONCLUSION: Phenobarbital (40 mg/kg) given in the first two hours of life in term neonates with perinatal asphyxia led to a decrease in CSF levels of lipid peroxides and antioxidant enzymes at 12 ± 2 hours of life.

[The correlation of asymmetrical dimethylarginine level and oxidative stress to the onset of Alzheimer's disease].

This study is to investigate the influence and mechanism of action of asymmetrical dimethylarginine (ADMA) and the induced oxidative stress level on Alzheimer's disease (AD) incidence. ADMA concentration, nitric oxide, Abeta(40)/Abeta(42) ratio, inducible NO synthase (iNOS) activity and the concentrations of the induced free radicals including malondialdehyde (MDA), 3-nitrotyrosine (3-NT) and peroxynitrite (ONOO-) in the cerebrospinal fluid (CSF) from 34 neurologically normal controls and 37 AD patients were quantitatively determined and statistically compared. The results showed that the ADMA concentration significantly decreased in AD patients, and it showed negative correlation with the NO, iNOS activity, and showed positive correlation with MMSE score. ADMA concentration was negatively correlated with Abeta(40)/Abeta(42) ratio (P<0.01) with the observation that Abeta(40)/Abeta(42) ratio increased while ADMA level decreased in CSF in AD patients. The concentration levels of MDA, 3-NT and ROS significantly increased compared with the control with all the P values less than 0.05. These findings suggested that the ADMA disorder and the oxidative damage effect of the induced free radicals in CSF of AD patients are an important mechanism of AD incidence, and their joint regulation may provide new idea for the prevention and clinical treatment of AD.

Prognostic value of biochemical markers of brain damage and oxidative stress in post-surgical aneurysmal subarachnoid hemorrhage patients.

The aim of this study is to determine effective biochemical markers and optimal sampling timing for prediction of neurological prognosis in post-surgical aneurysmal subarachnoid hemorrhage (SAH) patients. Subjects were a sequential group of SAH patients admitted to our centre who underwent aneurysm clipping before Day 3 and who received a cerebrospinal fluid (CSF) drain. CSF samples from 32 patients were collected on Days 3, 7, and 14. Neurological outcome was assessed by neurosurgeons using the Glasgow outcome scale (GOS) at 6 months after onset. CSF levels of neuron-specific enolase (NSE), S100B, and glial fibrillary acidic protein (GFAP) were determined using enzyme-linked immunosorbent assay, and the CSF concentrations of malondialdehyde (MDA) were determined using spectrophotometric assay. In univariate analysis, S100B on Days 3 and 14, GFAP on Days 3 and 7, and MDA on Day 14 were significantly higher in the poor outcome group (GOS 1-4) than in the good outcome group (GOS 5). In multivariate analysis, only MDA on Day 14 was identified as a significant predictor of poor neurological outcome at 6 months after onset. The area under the receiver-operating characteristic (ROC) curve for MDA on Day 14 was 0.841. For a threshold of 0.3 microM, sensitivity and specificity were 0.875 and 0.750, respectively. Our findings suggest that these biochemical markers, especially MDA, show significant promise as predictors of neurological outcome in clinical practice.

Linking neuron and skin: matrix metalloproteinases in amyotrophic lateral sclerosis (ALS).

Amyotrophic lateral sclerosis (ALS) mainly affects the motor neurons but may also include other organs such as the skin. We aimed to determine whether matrix metalloproteinases could provide a link between neuronal degeneration and skin alterations in ALS. We measured CSF, serum and skin tissue MMP-2 and MMP-9 using ELISA and malondialdehyde (MDA), a marker of lipid peroxidation, using High Performance Liquid Chromatography (HPLC) in 54 ALS patients and 36 controls. We found CSF and skin MMP-9 to be elevated in ALS as compared to controls (p<0.001, p=0.03, respectively). We observed CSF MMP-9 to be highest in patients with a rapid progressive course of disease (p=0.008). In contrast, we found no significant differences of CSF, serum or skin concentrations of MMP-2 as compared to controls. CSF MMP-2 concentrations decreased with duration of disease (p=0.04, R=-0.31). MDA was elevated in serum of ALS (p<0.001), though no correlation with MMP-2 or MMP-9 was observed. Our findings indicate a general upregulation of MMP-9 in ALS. MMP-9 seems to play a role in both neurodegeneration and skin changes in ALS and could thus be a common factor linking otherwise distant aspects of disease pathology.

Glutathione peroxidase and subarachnoid hemorrhage: implications for the role of oxidative stress in cerebral vasospasm.

OBJECTIVE: Worldwide, cerebral vasospasm after subarachnoid hemorrhage (SAH) has an estimated morbidity and mortality of 1.2 million annually. While it has long been suspected that reactive oxygen species play a major role in the etiology of cerebral vasospasm after SAH, promising results in animal work were not borne out in human clinical trials, despite intensive research effort. The purpose of this study is to investigate the role of glutathione peroxidase in the SAH cerebrospinal fluid milieu. METHODS: We utilized commercially available kits for the quantitation of glutathione peroxidase 1 (glutathione peroxidase) activity and oxygen radical capacity and sodium dodecyl sulfate polyacrylamide gel electrophoresis with Western blotting with specific antibodies to human glutathione peroxidase to determine the enzyme content of the cerebrospinal fluid samples. Human cerebrospinal fluid was obtained in an Institutional Review Board-exempt manner for this study in the following groups: control (no SAH), CSF(C) (SAH but no vasospasm on angiography) and CSF(V) (SAH with clinical and angiographic vasospasm). RESULTS: We found that glutathione peroxidase activity is significantly higher in CSF(V) compared with CSF(C), and this is reflected in a higher total oxidative capacity in CSF(V). Despite similar levels of glutathione peroxidase protein, CSF(V) had significantly greater activity than CSF(C). DISCUSSION: These results further elucidate previous research from this laboratory, showing increased oxidative stress in CSF(V) compared with CSF(C). In conclusion, there appears to be increased glutathione peroxidase activity in CSF(V), despite there being increased levels of oxidative stress markers, suggesting overwhelming oxidative stress may play a role in cerebral vasospasm after SAH.

Iron metabolism and lipid peroxidation products in infants with hypoxic ischemic encephalopathy.

BACKGROUND: Iron delocalization or misregulation of iron metabolism may play a critical role in the pathology of hypoxic ischemic encephalopathy (HIE). OBJECTIVE: To study iron metabolism and lipid peroxidation in newborn infants and to correlate non-protein-bound iron (NPBI) concentration with the severity of the post-asphyxial injury and subsequent short-term outcomes. STUDY DESIGN: Concentrations of NPBI and malondialdehyde (MDA) in the serum and in the cerebrospinal fluid (CSF) were measured in eight healthy newborn infants and nine newborn infants suffering from moderately severe HIE. Short-term outcomes (death, survival with or without neurological abnormality) were noted at hospital discharge. RESULT: Serum and CSF concentrations of both NPBI and MDA were significantly increased in HIE infants when compared to controls. Serum iron was significantly increased and total iron binding capacity was significantly decreased in HIE infants compared to controls. Out of the nine HIE infants, four infants died and two infants survived with abnormal neurological findings at hospital discharge. These six infants with clinical sequels had significantly increased concentrations of NPBI in the serum and in the CSF; and increased concentrations of MDA in the CSF when compared to the other three who survived without short-term abnormalities. CONCLUSION: We conclude that hypoxia ischemia alters iron metabolism and lipid peroxidation in newborn infants; and that NPBI and MDA in the CSF are increased in infants with HIE. This study supports a role for iron in oxidative injury to the central nervous system after hypoxic ischemic insults.

Oxidative stress in perinatal asphyxia.

Oxygen free radicals may cause tissue injury in perinatal asphyxia. We measured plasma and cerebrospinal fluid levels of malondialdehyde and plasma levels of glutathione peroxidase, catalase, and superoxide dismutase in 50 term newborns with perinatal asphyxia and eight newborns without asphyxia. Neonates with sepsis, major congenital malformations, and hemolytic disease were excluded. The levels of plasma and cerebrospinal fluid malondialdehyde, as well as of plasma glutathione peroxidase, catalase, and superoxide dismutase, were significantly higher in newborns with perinatal asphyxia, and demonstrated a progressive increase with greater severity of hypoxic ischemic encephalopathy. Higher levels of plasma and cerebrospinal fluid malondialdehyde and plasma catalase were documented in newborns who died from hypoxic ischemic encephalopathy, compared with those who survived, but no such difference was found in plasma levels of glutathione peroxidase and superoxide dismutase. The data of the present study suggest that, despite the increased activities of antioxidant enzymes in perinatal asphyxia, these neonates experience higher degrees of oxidative stress, as evidenced by increased levels of plasma and cerebrospinal fluid malondialdehyde. Hence, oxygen free radicals can be considered to play a significant role in the pathophysiology of perinatal asphyxia.

[Oxidative stress in victims with heavy combined cranium-facial trauma].

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.