Higher CSF Ferritin Heavy-Chain (Fth1) and Transferrin Predict Better Neurocognitive Performance in People with HIV.

HIV-associated neurocognitive disorder (HAND) remains prevalent despite antiretroviral therapy and involves white matter damage in the brain. Although iron is essential for myelination and myelin maintenance/repair, its role in HAND is largely unexplored. We tested the hypotheses that cerebrospinal fluid (CSF) heavy-chain ferritin (Fth1) and transferrin, proteins integral to iron delivery and myelination, are associated with neurocognitive performance in people with HIV (PWH). Fth1, transferrin, and the pro-inflammatory cytokines TNF-α and IL-6 were quantified in CSF at baseline (entry) in 403 PWH from a prospective observational study who underwent serial, comprehensive neurocognitive assessments. Associations of Fth1 and transferrin with Global Deficit Score (GDS)-defined neurocognitive performance at baseline and 30-42 months of follow-up were evaluated by multivariable regression. While not associated with neurocognitive performance at baseline, higher baseline CSF Fth1 predicted significantly better neurocognitive performance over 30 months in all PWH (p < 0.05), in PWH aged < 50 at 30, 36, and 42 months (all p < 0.05), and in virally suppressed PWH at all three visit time-points (all p < 0.01). Higher CSF transferrin was associated with superior neurocognitive performance at all visits, primarily in viremic individuals (all p < 0.05). All associations persisted after adjustment for neuro-inflammation. In summary, higher CSF Fth1 is neuroprotective over prolonged follow-up in all and virally suppressed PWH, while higher CSF transferrin may be most neuroprotective during viremia. We speculate that higher CSF levels of these critical iron-delivery proteins support improved myelination and consequently, neurocognitive performance in PWH, providing a rationale for investigating their role in interventions to prevent and/or treat HAND.

Evaluation of total, ceruloplasmin-associated and type II ferroxidase activities in serum and cerebrospinal fluid of multiple sclerosis patients.

Multiple sclerosis (MS) patients have increased brain iron deposition with higher oxidative stress (OxS). These two features can be caused by an inefficient removal of free iron from extracellular compartment. Ferroxidase activity (Feox) exerted by ceruloplasmin (FeoxCp) and by other molecules (FeoxII) appears to have a central role in this process. The aim of this study was to investigate serum and cerebrospinal fluid (CSF) total Feox, FeoxII and FeoxCp activities in MS patients and neurological controls. Serum and CSF Feox activity, FeoxII and FeoxCp activity was measured in 91 relapsing-remitting (RR) MS patients, 79 subjects with other inflammatory neurological disorders (OIND) and 65 with non-inflammatory neurological disorders (NIND), as controls. This study was approved by the Local Committee for Medical Ethics in Research. Serum total Feox activity was lower in MS group than in both NIND and OIND, with only the former control group differing significantly (p<0.001); FeoxII and FeoxCp activities were comparable among the groups. Serum Feox activities were not associated with disease activity as assessed by clinical examination or by Magnetic Resonance Imaging (MRI). Only total Feox activity was detectable in the CSF and was not different in MS compared to either OIND or NIND. In conclusion, a condition of low systemic Feox may increase the susceptibility of MS patients to iron(II) mediated-oxidative damage. This alteration is not reflected in CSF, suggesting that agents endowed with Feox activity might have different impact in iron homeostasis in the central nervous system compared to periphery.

[Prognostic value of the parameters of free radical oxidation in traumatic brain injury].

The dynamics of lipoperoxides content and activity of antioxidant (glutathione peroxidase, superoxide dismutase, catalase) and prooxidant (xanthine oxidase) enzymes were investigated in the blood and cerebrospinal fluid of patients with traumatic brain injury of various severity depending on the left- or right-hemisphere localization of injuries. Reciprocal relationship between lipid peroxidation and oxidative modification of proteins from first to 14th day, increase of the level of total antioxidant activity, accompanied with the growth of GP and catalase activity, against the background of decrease in SOD activity from 1 to 7 day have been revealed. Were set lower "average" content of lipid peroxides in the blood and cerebrospinal fluid of patients with the subsequent development of lethal results in compare with cases of favorable outcomes, decrease of geptanofilic lipid peroxides in serum below the reference level, as well as the reduction of antioxidant activity in the blood and cerebrospinal fluid, associated with a sharp falling in superoxide dismutase activity and a significant increase of xanthine oxidase activity, which preceded the lethal results.

[Decreased antioxidant-defence mechanisms in cerebrospinal fluid (CSF) in patients with tick-borne encephalitis (TBE)]. / Obnizenie mechanizmów obrony antyoksydacyjnej w plynie mózgowo-rdzeniowym u chorych z kleszczowym zapaleniem mózgu.

14 patients with Tick-borne Encephalitis (TBE) aged 21-64 (mean = 42.3) were analysed. The activity of superoxide dismutase (SOD), glutathione reductase (GSSG-R), glutathione peroxidase (GSH-Px), concentrations of malondialdehyde (MDA) and total sulphydryl groups (-SH) were measured in cerebrospinal fluid (CSF). Control group consisted of 10 patients whose CSF parameters remained in normal range. The CSF examination was performed twice: before and 3 weeks after treatment. The analysed activity of SOD, GSH-Px, GSSG-R, MDA and total sulphydryl groups (-SH) during the acute stage of the disease was significantly lower comparing to the control group. Despite the treatment, GSSG-R activity, MDA concentration and total sulphydryl groups--SH further lowered significantly. Although the SOD activity in CSF was higher in the second examination, it remained significantly lower comparing to the control group. We showed that the GSH-Px and GSSG-R activity in CSF after the acute stage of the TBE remained significantly lower than in the control group. Our examinations prove that during the TBE an increased generation of oxygen-derived free radicals occurs what shows decreased activity of the antioxidant parameters (SOD, GSH-Px, GSSG-R) and decreased concentration of total sulphydryl groups--SH in CSF. Our results suggest that during TBE, molecular structures injury of enzymes and antioxidative reactive cofactors may occur.

[Evaluation of oxidoreductive potential of patients with neuroborreliosis]. / Ocena potencjalu oksydoredukcyjnego u chorych z neuroborelioza.

AIM: The purpose of the study was to evaluate parameters of oxidoreductive system in serum and cerebrospinal fluid (CSF) of patients with neuroborreliosis. MATERIAL AND METHODS: The cases were 25 patients aged 21 to 64 (x = 42.3) hospitalized with diagnosis of neuroborreliosis. Activity of superoxide dismutase (Cu, Zn-SOD), glutathione reductase (GSSG-R), glutathione peroxidase (GSH-Px) and concentration of sulphydryl groups (-SH) and malondialdehyde (MDA) in serum and CSF were tested. The control group consisted of 10 patients with diagnosis of discopathy. An examination was performed twice: before and after treatment. RESULTS: Results of the study showed lack of stability in an oxidoreductive system during neuroborreliosis both in serum and in CSF. In CSF activity of SOD was increased while activity of GSH-Px and GSSG-R were decreased. Also concentration of -SH and lipid peroxidation products measured as MDA were increased. The increase of SOD, GSH-Px, GSSG-R activity and concentration of -SH and MDA in serum were detected. CONCLUSIONS: Disorders of an oxidoreductive system in CSF and serum during neuroborreliosis were observed. These changes persisted despite treatment and normalization of inflammatory CSF markers.

Serum and cerebrospinal fluid enzymes in subarachnoid haemorrhage.

Serum levels of creatine kinase (CK) and its isoenzyme CK-MB, lactate dehydrogenase (LDH), hydroxybutyric dehydrogenase (HBDH), glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were studied in 50 patients with subarachnoid haemorrhage. In 18 cases the cerebrospinal fluid (CSF) was also examined for total concentration of CK and CK-MB. The results were correlated with the degree of neurological deterioration, the angiographic spasm and prognosis. Concurrent increase of CK-MB, LDH and HBDH serum levels indicates a poor prognosis, whereas increase of GOT and GPT does not have clinical significance. High CK-MB levels in CSF were associated with the worst clinical evolution. However, increase of serum enzymes coincided in most cases with the appearance of the spasm. Monitoring of CK-MB, LDH and HBDH serum levels can be useful for following the evolution of the spasm and in predicting the outcome for patients with subarachnoid haemorrhage.

[Possible pathways of changes in the activity of a number of enzymes in spinal fluid in stroke]. / O vozmozhnykh putiakh izmeneniia aktivnosti riada fermentov v likvore pri mozgovykh insul'takh.

Examination of 234 cases with cerebral stroke showed that the activity of enzymes in the cerebrospinal fluid (CSF) of these patients increased as compared to the control group. In hemorrhagic strokes their activity was considerably higher than in ischemic ones. In 92 cases the results of examination were compared to sectional findings. The activity of enzymes was affected by numerous factors including the speed of stroke development, its nature, the size of the focus, the distance of the latter from the CSF pathways, and the severity of brain oedema.

[Effect of gamma-irradiation on the enzyme activity of cerebrospinal fluid lymphocytes in dogs]. / Vliianie gamma-oblucheniia na fermentativnuiu aktivnost' limfotsitov likvora sobak.

Cytochemical activity of succinate dehydrogenase (SDG), L-glycerophosphate dehydrogenase (L-GPDG), lactate dehydrogenase (LDG), and glutamate dehydrogenase (GDG) increased immediately after total-body irradiation with a dose of 129 mC/kg. After 2 h, LDG activity only returned to the control level. Irradiation of the head with the same dose caused less pronounced changes. Changes caused by lethal irradiation (1290 mC/kg) were different: there was an increase after exposure of the abdomen and a decrease in the activity of SDG and L-GPDG after irradiation of the head.