Myelin basic protein and neurofilament H in postmortem cerebrospinal fluid as surrogate markers of fatal traumatic brain injury.

The aim of this study was to investigate if the biomarkers myelin basic protein (MBP) and neurofilament-H (NF-H) yielded informative value in forensic diagnostics when examining cadaveric cerebrospinal fluid (CSF) biochemically via an enzyme-linked immunosorbent assay (ELISA) and comparing the corresponding brain tissue in fatal traumatic brain injury (TBI) autopsy cases by immunocytochemistry versus immunohistochemistry. In 21 trauma and 19 control cases, CSF was collected semi-sterile after suboccipital puncture and brain specimens after preparation. The CSF MBP (p = 0.006) and NF-H (p = 0.0002) levels after TBI were significantly higher than those in cardiovascular controls. Immunohistochemical staining against MBP and against NF-H was performed on cortical and subcortical samples from also biochemically investigated cases (5 TBI cases/5 controls). Compared to the controls, the TBI cases showed a visually reduced staining reaction against MBP or repeatedly ruptured neurofilaments against NF-H. Immunocytochemical tests showed MBP-positive phagocytizing macrophages in CSF with a survival time of > 24 h. In addition, numerous TMEM119-positive microglia could be detected with different degrees of staining intensity in the CSF of trauma cases. As a result, we were able to document that elevated levels of MBP and NF-H in the CSF should be considered as useful neuroinjury biomarkers of traumatic brain injury.

Cerebrospinal fluid myelin basic protein is elevated in multiple system atrophy.

INTRODUCTION: Parkinson's disease (PD) and multiple system atrophy (MSA) have overlapping symptoms, challenging an early diagnosis. Diagnostic accuracy is important because PD and MSA have a different prognosis and response to treatment. Here, we aimed to evaluate the diagnostic value of brain-specific structural proteins in cerebrospinal fluid (CSF) of PD and MSA patients, as well as their association with cognitive decline. METHODS: CSF samples were collected from patients with clear signs of parkinsonism, but with uncertain diagnosis at the time of inclusion. Clinical diagnoses of PD (n = 55) and MSA (n = 22) were established after 3 and 10 years of follow-up and re-evaluated after 12 years, according to the most updated clinical criteria. CSF from controls (n = 118) was studied for comparison. Neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B) and myelin basic protein (MBP) levels in CSF were measured using ELISA. Protein levels were also correlated with cognitive decline, i.e. worsening of the mini mental state examination (MMSE) over a period of three years. RESULTS: MBP concentrations were increased in MSA compared to PD and controls (p < 0.005) and could differentiate MSA and PD with high accuracy (AUC = 0.781; p < 0.001). Concentrations of MPB, GFAP and S100B, but not NSE, were significantly elevated in PD patients compared to controls (p = 0.05). None of the brain-specific structural proteins correlated with MMSE progression. CONCLUSIONS: Our results demonstrate that MBP differentiates PD from MSA at early stages of the disease, indicating that demyelination and axonal damage may already occur in early stages of MSA.

Extreme Diversity of IgGs Against Histones, DNA, and Myelin Basic Protein in the Cerebrospinal Fluid and Blood of Patients with Multiple Sclerosis.

It was recently shown that IgGs from sera of multiple sclerosis (MS) patients are active in the hydrolysis of DNA and myelin basic protein (MBP). We first analyzed the relative concentration of antibodies against five histones (H1, H2a, H2b, H3, and H4) in the cerebrospinal fluid (CSF) and serum of patients with MS. The relative concentrations of blood and CSF IgGs against histones and their activity in the hydrolysis of five histones varied greatly from patient to patient. However, all 28 IgG preparations were hydrolyzed from one to five histones. Relative activities and correlation coefficients among the activities of IgGs from serum and CSF in the hydrolysis of five histones (H1, H2a, H2b, H3, and H4), DNA, and MBP were calculated. It was shown that auto-IgGs from CSF and sera of MS patients are extremely heterogeneous in their affinity to histones, MBP, and DNA. The heterogeneity of IgG-abzymes hydrolyzing DNA, MBP, and histones from CSF and sera was also demonstrated using their isoelectrofocusing. The isofocusing profiles DNase, MBP-, and histone-hydrolyzing activities of IgGs may be very different for various individuals, but the total IgG subfractions with all their activities are distributed from pH 3 to 10.

Longstanding psychological stress in relation to biomarkers of neuronal dysfunction in cerebrospinal fluid: a 25-year follow-up study in women.

Longstanding psychological stress has been associated with increased risk of neurodegenerative disorders, such as dementia and Alzheimer's disease. In a prospective population study of women (n = 81), we tested if midlife stress (mean age 49 years) was associated with late-life biomarkers of neurodegeneration in cerebrospinal fluid (CSF) (mean age 74 years) in linear regression models. It was found that women who report of stress at baseline (n = 20) had higher levels of CSF visinin-like protein-1 (VILIP-1) (age adjusted ß = 0.113, p = 0.017) and CSF myelin basic protein (ß = 0.060, p = 0.030) compared with women without midlife stress (n = 61). There was also a trend observed for higher CSF neurofilament light (ß = 0.133, p = 0.056). In addition, longer periods of stress (i.e., stress at 2-3 midlife examinations) were associated with higher levels of CSF VILIP-1. The results suggest that longstanding stress might be associated with neurodegenerative processes in the brain, as CSF VILIP-1 is an unspecific marker for neuronal injury and CSF myelin basic protein reflects neuroaxonal demyelination.

Brain-originated peptides as possible biochemical markers of traumatic brain injury in cerebrospinal fluid post-mortem examination.

The release of brain-originated peptides such as tau protein (MAPT), S-100ß, neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP) into the cerebrospinal fluid (CSF) has been positively correlated with head injuries in clinical and basic research. In this study, we wanted to examine if selected CSF biomarkers (GFAP, NFL, and myelin basic protein - MBP) of head injury may be useful in post-mortem examination and diagnosis of forensic cases. The study was carried out using cases of head injury and cases of sudden death (cardiopulmonary failure, no injuries of the head as control group) provided by forensic pathologists at the Department of Forensic Medicine, Medical University of Warsaw. Cerebrospinal fluid was collected within 24 h after death using suboccipital puncture. The concentration of these peptides was compared using an enzyme-linked immunosorbent assay (ELISA). Brain specimens (frontal cortex) were collected during forensic autopsies. Sections were stained immunohistochemically against GFAP, MBP, NF, and amyloid-ß precursor protein (APP). As a result we documented that elevated levels of CSF, GFAP, MBP, and NFL should be considered a marker for severe and moderate traumatic brain injury. Elevated levels of those peptides combined with a negative APP staining point to their role as markers of head trauma with a shorter time span than APP (manner of minutes).

Novel SPG11 Mutations in a Patient with Symptoms Mimicking Multiple Sclerosis.

We describe the cases of two sisters with spastic paraplegia 11 (SPG11). The younger sister developed relapsing lesions in the brain white matter with enhancement during the acute phase that mimicked multiple sclerosis (MS). The elevation of myelin basic protein in the cerebrospinal fluid (CSF) suggested demyelination, but a normal IgG index, the absence of oligoclonal bands, and the ineffectiveness of steroid treatment indicate that an autoimmune mechanism may not have been involved. In these affected sisters, we identified novel compound heterozygous mutations in the SPG11 gene. Our cases indicate the possible existence of a broader phenotypic spectrum of SPG11 mutations.

Cerebrospinal fluid orexin-A levels in systemic lupus erythematosus patients presenting with excessive daytime sleepiness.

Objective Involvement of the hypothalamus is rare in patients with systemic lupus erythematosus (SLE). In this study, we measured cerebrospinal fluid (CSF) orexin-A levels in SLE patients with hypothalamic lesions to investigate whether the orexin system plays a role in SLE patients with hypothalamic lesions who present with excessive daytime sleepiness (EDS). Methods Orexin-A levels were measured in CSF from four patients with SLE who presented with hypothalamic lesions detected by MRI. Three patients underwent repeated CSF testing. All patients met the updated American College of Rheumatology revised criteria for SLE. Results Tests for serum anti-aquaporin-4 antibodies, CSF myelin basic protein and CSF oligoclonal bands were negative in all patients. All patients presented with EDS. Low to intermediate CSF orexin-A levels (92-180 pg/ml) were observed in three patients in the acute stage, two of whom (patients 1 and 2) underwent repeated testing and showed increased CSF orexin-A levels, reduced abnormal hypothalamic lesion intensities detected by MRI and EDS dissipation at follow-up. In contrast, CSF orexin-A levels were normal in one patient (patient 4) while in the acute stage and at follow-up, despite improvements in EDS and MRI findings. Patient 4 showed markedly increased CSF interleukin-6 levels (1130 pg/ml) and a slightly involved hypothalamus than the other patients. Conclusions Our findings suggest that the orexinergic system has a role in EDS in SLE patients with hypothalamic lesions. Furthermore, cytokine-mediated tissue damage might cause EDS without orexinergic involvement.

Axonal damage is remarkable in patients with acutely worsening symptoms of compression myelopathy: biomarkers in cerebrospinal fluid samples.

PURPOSE: To determine levels of biomarkers reflecting damage to axon, myelin, astrocytes, and neuron in cerebrospinal fluid (CSF) of patients with cervical compression myelopathy. METHODS: We collected 69 CSF samples from patients before spinal surgery for acutely worsening compression myelopathy (AM, 20), chronic compression myelopathy (CM, 20), and lumbar canal stenosis (LCS 29; control). We measured levels of phosphorylated neurofilament subunit H (pNF-H), tau (reflecting axonal damage), myelin basic protein (MBP) (reflecting demyelination), S100b (reflecting astrocyte damage), and neuron-specific enolase (NSE) (reflecting neuronal damage). Change of neurological function by surgery was determined using a Japanese Orthopaedic Association (JOA) score for cervical myelopathy. RESULTS: Significantly higher levels of pNF-H were detected in AM compared with those in either CM or LCS (P < 0.01). Significantly higher levels of tau were detected in AM compared with those in CM (P < 0.05). Levels of MBP were undetectable in almost all the patients. Levels of S100b were equivalent in the three groups. Levels of NSE in AM and CM were significantly lower than those in LCS (P < 0.01). The recovery rate of JOA score was significantly greater for patients with AM than CM. We found a positive correlation between pNF-H and recovery of JOA score (r = 0.381, P = 0.018). CONCLUSION: The present results suggest that axonal damage is remarkable compared with demyelination, astrocytic, and neuronal damage in AM. Better clinical outcome in AM with high CSF levels of pNF-H indicates that axonal compensatory plasticity in spinal cord is preserved, and pNF-H can be predictive of good surgical outcome for AM. These slides can be retrieved under Electronic Supplementary Material.

Two-Year Follow-Up Magnetic Resonance Imaging and Spectroscopy Findings and Cerebrospinal Fluid Analysis of a Dog with Sandhoff's Disease.

A 13-month-old female Toy Poodle was presented for progressive ataxia and intention tremors of head movement. The diagnosis of Sandhoff's disease (GM2 gangliosidosis) was confirmed by deficient ß-N-acetylhexosaminidase A and B activity in circulating leukocytes and identification of the homozygous mutation (HEXB: c.283delG). White matter in the cerebrum and cerebellum was hyperintense on T2-weighted and fluid-attenuated inversion recovery magnetic resonance images. Over the next 2 years, the white matter lesions expanded, and bilateral lesions appeared in the cerebellum and thalamus, associated with clinical deterioration. Magnetic resonance spectroscopy showed progressive decrease in brain N-acetylaspartate, and glycine-myo-inositol and lactate-alanine were increased in the terminal clinical stage. The concentrations of myelin basic protein and neuron specific enolase in cerebrospinal fluid were persistently increased. Imaging and spectroscopic appearance correlated with histopathological findings of severe myelin loss in cerebral and cerebellar white matter and destruction of the majority of cerebral and cerebellar neurons.

LEVELS OF NEUROSPECIFIC MARKERS IN CEREBROSPINAL FLUID OF ADULT PATIENTS WITH BACTERIAL MENINGITIS.

At present, the great attention is given to the neurospecific markers as their elevated level in the cerebrospinal fluid corresponds to the degree of destruction of relevant CNS cells. Therefore, actual direction of the studies of the pathogenesis and diagnosis of CNS diseases is to determine levels of neurospecific markers in the cerebrospinal fluid (CSF). The purpose of the study was to evaluate the diagnostic and prognostic role of NSE, S-100 protein, GFAP and MBP levels in CSF of patients with acute bacterial meningitis. S-100 protein, NSE, GFAP and MBP levels in CSF of patients with acute pneumococcal and meningococcal meningitis were determined during admission and after 10-12 days of treatment. Patients were divided into groups depending on the etiology and severity of the disease. 60 cases of acute bacterial meningitis, as a study group, and 12 cases with acute respiratory infection and meningism, as a control group, were analyzed. It is shown that CSF levels of NSE, S-100 protein, GFAP and MBP on the first day of admission were significantly increased (P<0,05), depending on the severity of the disease. The highest levels of neurospecific markers have been identified in non-survivors (P<0,001). The concentration changes of CSF neurospecific markers are found to be helpful as a diagnostic and prognostic marker in acute bacterial meningitis.

Is myelin basic protein a potential biomarker of brain cancer?

Myelin basic protein is a potential biomarker for the central nervous system diseases in which the myelin sheath is destroyed. Using pseudo-selected reaction monitoring and the method of standard additions, we have measured the myelin basic protein level in the cerebrospinal fluid of patients with neurotrauma (n = 6), chronic neurodegenerative diseases (n = 2) and brain cancer (n = 5). Myelin basic protein was detected only in four out of five cerebrospinal fluid samples of patients with brain cancer. The cerebrospinal fluid myelin basic protein level ranged from 3.7 to 8.8 ng ml-1. We suggest that monitoring of myelin basic protein in cerebrospinal fluid can serve as a diagnostic test for the brain cancer.

The cerebrospinal fluid in multiple sclerosis: far beyond the bands.

The cerebrospinal fluid analysis has been employed for supporting multiple sclerosis diagnosis and ruling out the differential diagnoses. The most classical findings reflect the inflammatory nature of the disease, including mild pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G, and, most typically, the presence of oligoclonal bands. In recent years, new biomarkers have emerged in the context of multiple sclerosis. The search for new biomarkers reflect the need of a better evaluation of disease activity, disease progression, and treatment efficiency. A more refined evaluation of disease and therapy status can contribute to better therapeutic choices, particularly in escalation of therapies. This is very relevant taking into account the availability of a greater number of drugs for multiple sclerosis treatment in recent years. In this review, we critically evaluate the current literature regarding the most important cerebrospinal fluid biomarkers in multiple sclerosis. The determination of biomarkers levels, such as chemokine ligand 13, fetuin A, and mainly light neurofilament has shown promising results in the evaluation of this disease, providing information that along with clinical and neuroimaging data may contribute to better therapeutic decisions. RESUMO A análise do líquido cefalorraquidiano tem sido empregada para avaliação diagnóstica da esclerose múltipla e a exclusão dos diagnósticos diferenciais. Os achados clássicos refletem a natureza inflamatória da doença, incluindo discreta pleocitose, leve hiperproteinorraquia, aumento da síntese intratecal de imunoglobulina G e, mais tipicamente, a presença de bandas oligoclonais. Nos últimos anos, surgiram novos biomarcadores para esclerose múltipla, e esta busca por marcadores reflete a necessidade de melhor avaliar a atividade e a progressão da doença, bem como a eficácia terapêutica. Uma avaliação mais refinada da atividade da doença e da resposta aos medicamentos pode contribuir para melhores decisões terapêuticas, particularmente no que se refere à troca de medicação. Isto é muito importante nos dias de hoje, quando surgem novas opções medicamentosas. Neste artigo de revisão, avaliamos criticamente a literatura atual referente aos novos marcadores liquóricos na esclerose múltipla. A mensuração destes marcadores, como a quimiocina CXCL13, fetuína A e, principalmente, o neurofilamento de cadeia leve, demonstrou resultados promissores na avaliação da doença, provendo informações que, em conjunto com dados clínicos e de neuroimagem, podem contribuir para melhores decisões terapêuticas.

Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization-case study.

Despite the effective suppression of viremia with antiretroviral therapy, HIV can still replicate in the central nervous system (CNS). This was a longitudinal study of the cerebrospinal fluid (CSF) and serum dynamics of several biomarkers related to inflammation, the blood-brain barrier, neuronal injury, and IgG intrathecal synthesis in serial samples of CSF and serum from a patient infected with HIV-1 subtype C with CNS compartmentalization.The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation sequencing and F-statistics analysis of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples. The CSF biomarker analysis in this patient showed that symptomatic CSF escape is accompanied by CNS inflammation, high levels of cell and humoral immune biomarkers, CNS barrier dysfunction, and an increase in neuronal injury biomarkers with demyelization. Independent and isolated HIV replication can occur in the CNS, even in HIV-1 subtype C, leading to compartmentalization and development of quasispecies distinct from the peripheral plasma. These immunological aspects of the HIV CNS escape have not been described previously. To our knowledge, this is the first report of CNS HIV escape and compartmentalization in HIV-1 subtype C.

The cerebrospinal fluid in multiple sclerosis: far beyond the bands / O líquido cefalorraquidiano na esclerose múltipla: muito além das bandas

ABSTRACT The cerebrospinal fluid analysis has been employed for supporting multiple sclerosis diagnosis and ruling out the differential diagnoses. The most classical findings reflect the inflammatory nature of the disease, including mild pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G, and, most typically, the presence of oligoclonal bands. In recent years, new biomarkers have emerged in the context of multiple sclerosis. The search for new biomarkers reflect the need of a better evaluation of disease activity, disease progression, and treatment efficiency. A more refined evaluation of disease and therapy status can contribute to better therapeutic choices, particularly in escalation of therapies. This is very relevant taking into account the availability of a greater number of drugs for multiple sclerosis treatment in recent years. In this review, we critically evaluate the current literature regarding the most important cerebrospinal fluid biomarkers in multiple sclerosis. The determination of biomarkers levels, such as chemokine ligand 13, fetuin A, and mainly light neurofilament has shown promising results in the evaluation of this disease, providing information that along with clinical and neuroimaging data may contribute to better therapeutic decisions.

RESUMO A análise do líquido cefalorraquidiano tem sido empregada para avaliação diagnóstica da esclerose múltipla e a exclusão dos diagnósticos diferenciais. Os achados clássicos refletem a natureza inflamatória da doença, incluindo discreta pleocitose, leve hiperproteinorraquia, aumento da síntese intratecal de imunoglobulina G e, mais tipicamente, a presença de bandas oligoclonais. Nos últimos anos, surgiram novos biomarcadores para esclerose múltipla, e esta busca por marcadores reflete a necessidade de melhor avaliar a atividade e a progressão da doença, bem como a eficácia terapêutica. Uma avaliação mais refinada da atividade da doença e da resposta aos medicamentos pode contribuir para melhores decisões terapêuticas, particularmente no que se refere à troca de medicação. Isto é muito importante nos dias de hoje, quando surgem novas opções medicamentosas. Neste artigo de revisão, avaliamos criticamente a literatura atual referente aos novos marcadores liquóricos na esclerose múltipla. A mensuração destes marcadores, como a quimiocina CXCL13, fetuína A e, principalmente, o neurofilamento de cadeia leve, demonstrou resultados promissores na avaliação da doença, provendo informações que, em conjunto com dados clínicos e de neuroimagem, podem contribuir para melhores decisões terapêuticas.

CSF YKL-40 and GAP-43 are related to suicidal ideation in older women.

OBJECTIVE: To investigate possible relationships between suicidal ideation and cerebrospinal fluid (CSF) levels of glial markers YKL-40 (also known as chitinase-3-like protein 1), growth-associated protein-43 (GAP-43) and myelin basic protein (MBP). METHOD: The sample was obtained from the Prospective Population Study of Women and included 86 women without dementia who underwent both psychiatric examinations and lumbar puncture (LP). Eight of these women reported past-month suicidal ideation. RESULTS: Significantly, higher CSF levels of both YKL-40 and GAP-43 were detected in women with past-month suicidal ideation. Associations with suicidal ideation remained for both YKL-40 and GAP-43 in regression models adjusted for smoking status, BMI and age. CSF levels of YKL-40, GAP-43 and MBP did not differ by depression status. Higher levels of CSF GAP-43 were associated with feelings of worthlessness; a strong relationship was demonstrated in the fully adjusted model (OR 5.95 CI [1.52-23.20], P = 0.01). CONCLUSION: Our findings of elevated CSF concentrations of both YKL-40 and GAP-43 in women with suicidal ideation, compared to those without, suggest that a disrupted synaptic glial functioning and inflammation may be related to the aetiology of suicidal ideation in older adults.

Preclinical amyloid pathology biomarker positivity: effects on tau pathology and neurodegeneration.

Brain autopsy and biomarker studies indicate that the pathology of Alzheimer's disease (AD) is initiated at least 10-20 years before clinical symptoms. This provides a window of opportunity to initiate preventive treatment. However, this emphasizes the necessity for biomarkers that identify individuals at risk for developing AD later in life. In this cross-sectional study, originating from three epidemiologic studies in Sweden (n=1428), the objective was to examine whether amyloid pathology, as determined by low cerebrospinal fluid (CSF) concentration of the 42 amino acid form of ß-amyloid (Aß42), is associated with biomarker evidence of other pathological changes in cognitively healthy elderly. A total of 129 patients were included and CSF levels of Aß42, total tau, tau phosphorylated at threonine 181 (p-tau), neurogranin, VILIP-1, VEGF, FABP3, Aß40, neurofilament light, MBP, orexin A, BDNF and YKL-40 were measured. Among these healthy elderly, 35.6% (N=46) had CSF Aß42 levels below 530 pg ml-1. These individuals displayed significantly higher CSF concentrations of t-tau (P<0.001), p-tau (181) (P<0.001), neurogranin (P=0.009) and FABP3 (P=0.044) compared with amyloid-negative individuals. Our study indicates that there is a subpopulation among healthy older individuals who have amyloid pathology along with signs of ongoing neuronal and synaptic degeneration, as well as tangle pathology. Previous studies have demonstrated that increase in CSF tau and p-tau is a specific sign of AD progression that occurs downstream of the deposition of Aß. On the basis of this, our data suggest that these subjects are at risk for developing AD. We also confirm the association between APOE ɛ4 and amyloid pathology in healthy older individuals.

Simultaneous quantification of Myelin Basic Protein and Tau proteins in cerebrospinal fluid and serum of Multiple Sclerosis patients using nanoimmunosensor.

This study was aimed at the development of an immunosensor for the simultaneous quantification of Myelin Basic Protein (MBP) and Tau proteins in cerebrospinal fluid (CSF) and serum, obtained from Multiple Sclerosis (MS) patients. The newly developed GO/pPG/anti-MBP/anti-Tau nanoimmunosensor has been established by immobilization of MBP and Tau antibodies. The newly developed nanoimmunosensor was tested, optimized and characterized using differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). The developed nanoimmunosensor was seen to have detection limits of 0.30nM for MBP and 0.15nM for Tau proteins which were sufficient for the levels to be analysed in neuro-clinic. The clinical study performed using CSF and serum of MS patients showed that the designed nanoimmunosensor was capable of detecting the proteins properly, that were essentially proven by ELISA.

Biochemical manifestations of the nervous tissue degradation after the blood-brain barrier opening or water intoxication in rats.

OBJECTIVES: The aim of the study was to determine changes of biomarkers of nervous tissue degradation in experimental model of osmotic blood-brain barrier opening or water intoxication and to find whether they correspond to changes in well defined clinical entities. METHODS: In the cerebro-spinal fluid taken via the suboccipital puncture, myelin basic protein (MBP ng/ml), neuron-specific enolase (NSE ng/ml) and TAU-protein (Tau pg/ml) were determined by ELISA in 19 controls and 29 experimental rats several hours or one week after the experimental intervention. RESULTS: Significant difference between the control and experimental groups was revealed only for the concentration of myelin basic protein. After the BBB opening, its level dramatically increased within hours and dropped back to control values within one week. Water intoxication induced only dilutional hypoproteinorachia. No significant changes were found in NSE and levels of TAU-protein were not detectable. CONCLUSION: 1. Increased permeability of cytoplasmic membranes induced by water intoxication does not alter any of monitored CSF biomarkers. 2. Osmotic opening of the BBB in vivo experiment without the presence of other pathological conditions leads to a damage of myelin, without impairment of neurons or their axons.

Comparison of Antibodies with Amylase Activity from Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis.

We have recently shown that IgGs from serum and cerebrospinal fluid (CSF) of MS patients are active in hydrolysis of DNA and myelin basic protein. According to literature data, anti-DNA and anti-MBP abzymes may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development. At the same time, the involvement of antibodies with amylase activity in the pathogenesis of any autoimmune disease has not yet been identified. Electrophoretically and immunologically homogeneous IgGs were obtained by a sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We are able to present the first unpredictable evidence showing that IgGs from CSF possess amylase activity and efficiently hydrolyze maltoheptaose; their average specific Ab activity is ~30-fold higher than that of antibodies from sera of the same MS patients. Specific average RA (SAA) for IgGs from healthy volunteers was approximately ~1000 lower than that for MS patients. In addition, it was shown that a relative SAA of total proteins of CSF (including Abs) ~15-fold lower than that for purified IgGs, while the relative SAA of the total sera protein is higher than that of sera IgGs by a factor of 1033. This result speaks in favor of the fact that amylolytic activity of CSF proteins is mainly caused by the activity of amylase abzymes. One cannot exclude, that amylase abzymes of CSF can play a, as yet unknown, role in the pathogenesis of MS. Some possible reasons of these findings are discussed.