Myelin Basic Protein Concentration Research Articles

Electroacupuncture Therapy Effectively Protects the Rat Brain after Intracerebral Hemorrhage

Objective. Electroacupuncture (Ea) is a useful complementary and alternative therapy for intracerebral hemorrhage (ICH). However, the neurobiological basis for the Ea treatment of ICH is still unclear. The primary aim of the present study was to explore whether Ea prevents brain edema, apoptosis, excitotoxicity, and neuroinflammation in rats after hemorrhagic stroke. Methods. Rats were randomly divided into Sham, Control, and Ea groups. We used modified neurological severity score (mNSS) and gait analysis to estimate neurological function in rats, and PET/CT to assess glucose uptake and the hemorrhagic focus volume. Measurement of the brain water content and TUNEL staining were used to evaluate brain edema and cell apoptosis, respectively. The serum myelin basic protein (MBP), neuron-specific enolase (NSE), calcium-binding protein B (S100B), and tumor necrosis factor-α (TNF-α) concentrations were examined with ELISA. The expression levels of the CD68, GALC, Arg-1, iNOS, NR2A, Glu2R, AQP4, MAP2, GFAP, AQP9, Bcl-2, Bax, and Glu proteins around the hematoma were detected via immunohistochemistry staining. Western blot was used to analyze the levels of the AQP4, AQP9, Bax, Bcl-2, iNOS, and Arg-1 proteins. Results. Ea treatment improved neurological function and reduced the hemorrhagic area and brain water content in rats after ICH. The serum concentrations of MBP, NSE, S100B, and TNF-α all decreased significantly in the Ea group compared with the Control group. Expression levels of the Glu, NR2A, AQP4, AQP9, Bax, GFAP, iNOS, and CD68 proteins in brain tissue surrounding the hematoma were obviously suppressed in ICH rats following Ea treatment. Moreover, Ea stimulation increased the levels of the MAP2, GALC, Glu2R, Arg-1, and Bcl-2 proteins, but reduced the number of TUNEL-positive cells in rats after ICH. Conclusion. The results of this study suggest that Ea may exert neuroprotective effects by suppressing brain edema, apoptosis, excitotoxicity, and neuroinflammation.

Serum tau protein and myelin basic protein in pediatric patients with congenital heart defects undergoing cardiac surgery: preliminary assessment as novel neuromarkers of brain injury.

Neurological impairment is a big concern in the development of patients with congenital heart defects (CHD). A number of neuromarkers have been studied in search of a diagnostic or prognostic marker for brain injury during the vulnerable perioperative period. Our aim was to assess two novel neuromarkers, myelin basic protein (MBP) and protein Tau (pTau), as diagnostic markers for brain injury in perioperative period in children with CHD. Forty patients were enrolled and dichotomized based on peripheric oxygen saturation in cyanotic and non-cyanotic group. Blood samples were collected preoperative, after the induction of anesthesia, and in postoperative day 1. Neuromarker concentrations were measured using commercially available ELISA kits. Neuromarkers' values were increased postoperative, with statistical significance reached only in non-cyanotic group (p < 0.0001). A significant positive correlation was observed between preoperatory MBP and albumin level, hemoglobin level, height, and weight of patients. Association with cerebral saturations were analyzed by a coefficient defined as ≥ 20% reduction in cerebral saturation measured by near-infrared spectroscopy during perioperative period. An acceptable predicting model was observed with pTau in cyanotic group (AUC = 0.7). We evaluated MBP and pTau as potential biomarkers of brain injury in children with CHD undergoing cardiac surgery. Elevated postoperative pTau and MBP concentrations were observed in both groups. Elevated pTau values were associated with perioperative hypoxemia.

Hyperoxia Induced Hypomyelination.

We asked whether hyperoxia might induce hypomyelination of the corpus callosum, clinically described as periventricular leukomalacia (PVL) of the severely preterm infant. Mouse pups and their nursing dams were placed in 80% oxygen from P4-P8, then removed to room air until P11. Corpus callosal sections were probed myelin immunofluorescence, tested for myelin basic protein concentration by Western blot, and both glial fibrillary acidic protein levels and apoptosis quantified. Density of corpus callosal capillaries were measured after lectin staining and hypoxia measured by Hypoxyprobe. Numbers of oligodendrocytes were quantified by immunohistochemistry. We next used hypoxiamimesis as a surrogate to hypoxia by comparing cerebral hypoxia inducible factor (HIF) stabilization to hepatic HIF stabilization. Hyperoxia induced hypomyelination and a reduction of corpus callosal capillaries. Hyperoxia decreased numbers of oligodendrocytes with an increase in corpus callosal fibrosis and apoptosis. Cerebral hypoxiamimesis induced hypomyelination whereas hepatic hypoxiamimesis alone increased myelination, oligodendrocyte numbers, and corpus callosal capillary density. Hepatic HIF-1 dependence on myelination was confirmed using the cre/lox hepatic HIF-1 knockout. These findings suggest that hyperoxia can induce hypomyelination through vasoobliteration and subsequent ischemia, adding a potential oxygen induced mechanism to the diverse causes of periventricular leukomalacia of the severely preterm infant. Targeting hepatic HIF-1 alone led to increased myelination.

Relationship between cerebrospinal fluid biomarkers of inflammation and tissue damage in primary progressive multiple sclerosis

Background and ObjectivesIt is unclear to what extent intrathecal inflammation contributes to the pathogenesis in primary progressive multiple sclerosis (PPMS). We conducted an exploratory study to investigate the degree of intrathecal inflammation and its association with biomarkers of disease activity and severity in patients with PPMS. MethodsWe included patients with PPMS who participated in a randomized controlled trial conducted at the Danish Multiple Sclerosis Center, patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls. We analyzed concentrations of a panel of cytokines in CSF using electrochemiluminescence assays. We then explored the relationship between cytokines found in increased CSF concentrations in patients with PPMS (compared with healthy controls) with CSF concentrations of neurofilament light chain (NFL) and myelin basic protein (MBP), IgG-index, and magnetic resonance imaging (MRI) metrics (volume, magnetization transfer ratio and diffusion tensor imaging) from lesions, normal-appearing white matter, and cortical grey matter. ResultsWe included 59 patients with PPMS, 40 patients with RRMS, and 21 healthy controls. In patients with PPMS, CSF concentrations of CC chemokine ligand 3 (CCL-3), CXC chemokine ligand 8 (CXCL-8), CXCL-10, interleukin (IL)-10, IL-15, and vascular endothelial growth factor (VEGF)-A were increased compared with healthy controls and comparable with CSF concentrations in patients with RRMS. In addition, patients with PPMS had increased CSF concentrations of IL-12p40, IL-17A, tumor necrosis factor (TNF)-α, and lymphotoxin (LT)-α compared with healthy controls, but concentrations of these cytokines were even higher in patients with RRMS. For the remaining seven cytokines (CCL22, interferon-γ, IL-5, IL-7, IL-16, IL-22, IL-27), we found no difference between patients with PPMS and healthy controls. CSF concentrations of NFL and MBP correlated weakly with concentrations of IL-15, while the remaining proinflammatory cytokines were not associated with CSF concentrations of NFL or MBP. The IgG-index correlated with four cytokines (IL-10, IL-12p40, TNF-α, and LT-α). We did not observe any significant associations between MRI metrics and CSF biomarkers of inflammation. DiscussionIn this exploratory study, we found few and weak associations between intrathecal inflammation and the extent of neuroaxonal damage and demyelination, and no associations between intrathecal inflammation and MRI metrics, in patients with PPMS. Our findings suggest that, for patients with PPMS, these measures of intrathecal inflammation are not associated with the extent of neuroaxonal injury, demyelination, and disease severity, and these processes may therefore have less relevance in PPMS than in relapsing forms of MS.

Distribution of five clinically important neuroglial proteins in the human brain

Glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), neurofilament light chain (NFL), tau and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) are five neuroglial proteins that are used as CSF or blood biomarkers of tissue damage in the nervous system. There is incomplete knowledge of how the concentration of these proteins differs between anatomical regions in the CNS as previous studies have focused on gene expression or non-quantitative protein analyses, limiting the interpretability of these biomarkers. The purpose of this study was to create a map of the tissue content of these proteins in different regions of the CNS. The concentrations of the investigated proteins were determined with ELISA in post mortem tissue homogenates from 17 selected anatomical regions in the CNS from ten deceased donors aged 24 to 50 years. When appropriate, the protein concentrations were adjusted for post-mortem interval. In total, 168 tissue samples were analysed. There was a substantial variation in the concentrations of GFAP, MBP, NFL, tau and UCHL1 between different CNS regions. Highly myelinated areas of the CNS had tenfold higher MBP concentration than cerebral cortex, whereas tau showed an inverse pattern. GFAP, NFL and tau displayed an anteroposterior gradient in cerebral white matter. The cerebellum had low concentrations of all the investigated proteins. In conclusion, the tissue concentrations of GFAP, MBP, NFL, tau and UCHL1 were determined throughout the CNS. This information can be used as a reference when interpreting circulating levels of these biomarkers in relation to the extent and localisation of CNS-damaging processes.

Estimation of Myelin Basic Protein Levels in Natural Cases of Canine Distemper Encephalomyelitis

Background: Canine distemper virus (CDV) affects both white and grey matter in the central nervous system (CNS). It causes demyelination of white matter tracts, which releases myelin basic protein (MBP) into the cerebrospinal fluid (CSF). MBP levels in CSF could therefore indirectly indicate the extent of white matter damage. The objective of this study was to determine MBP levels in the CSF of dogs infected with natural cases of neurologic distemper. Methods: In this study samples from healthy dogs, clinical cases of CDV and stray dogs from in and around the institute were collected for investigation. The infection of the CNS was established by estimating the albumin quotient and, for 16 cases, by histopathology. CSF biochemical parameters were analysed for 35 sero-positive clinical cases of neurologic distemper. MBP levels in samples were estimated by quantitative ELISA. Stray dogs (6 cases) were also screened for this purpose. Result: MBP levels in CSF were significantly (p≤0.05) increased in natural cases of distemper encephalomyelitis and stray dogs relative to controls. Three of the neurologic distemper cases clinically recovered despite high MBP levels, and two stray dogs also had higher MBP concentrations. High CSF MBP may therefore not be a useful marker for predicting the outcome of neurologic distemper.

Analysis of the risk of traumatic brain injury and evaluation neurogranin and myelin basic protein as potential biomarkers of traumatic brain injury in postmortem examination.

In forensic pathology, traumatic brain injury (TBI) is a frequently encountered cause of death. Unfortunately, the statistic autopsy data, risk investigation about injury patterns, and circumstances of TBI are still sparse. Estimates of survival time post-TBI and postmortem diagnosis of TBI are especially important implications in forensic medicine. Neurogranin (Ng) and myelin basic protein (MBP) represent potential biomarkers of TBI. The present study analyzed retrospectively the forensic autopsy records of TBI cases at a university center of medico-legal investigation from 2008 to 2020. Immunohistochemistry and enzyme-linked immunosorbent assays (ELISA) were used to investigate the expression changes of Ng and MBP in the cortical brain injury adjacent tissues and serum, respectively, from cases of TBI at autopsy with different survival times post-TBI. The results show that the major mechanism of death of TBI is assault, and accident was the major manner of death. Ng and MBP are mainly expressed in the cortical nerve cells and the myelin sheath, respectively. The serum levels of Ng and MBP in each TBI group were higher compared with those in the controls. The brain cortical levels of Ng and MBP decreased at first and then steadily increased with extended survival time post-TBI. The immunopositive ratios and serum concentration of Ng and MBP have shown significant differences among control group and all TBI group (p < 0.001). Collectively, the immunohistochemical analyses of Ng and MBP in human brain tissues may be useful to determine the survival time after TBI, and Ng and MBP level in the human blood specimens could be considered as a postmortem diagnostic tools of TBI in forensic practice.

Serum Concentration of Myelin Basic Protein as a Prognostic Marker in Mild-to-moderate Head Injury Patients: A Prospective Study in a Tertiary Care Center

Abstract Objective To estimate the level of myelin basic protein (MBP) and look for its validity in outcome prediction among mild-to-moderate head injury patients. Materials and Methods It was a prospective study done at the Department of Neurosurgery, Institute of Medical Sciences, Banaras Hindu University from Jan 2018 to July 2019. All patients who presented to us within 48 hours of injury with mild-to-moderate head injury with apparently normal CT brain were include in the study. The serum sample were collected on the day of admission and 48 hours later, and patients were treated with standard protocols and observed 6 months postdischarge. Results Of the 32 patients enrolled, we observed mean MBP level was higher for severity of brain damage, but not associated with age, mode of injury, and radiological diagnosis. Mean MBP levels were not statistically associated with Glasgow coma scale (GCS) score at admission but was correlated to outcome with p &lt; 0.05, with sensitivity of 50% and specificity 72%, that is, patients with good outcome have lower mean MBP levels. Conclusion MBP as per our analysis can be used as a prognostic marker in patients with head injury. It is not the absolute value rather a trend showing rise in serum MBP levels, which carries a significant value in outcome prediction.

Noncovalent Association and Partitioning of Some Perfume Components at Infinite Dilution with Myelin Basic Protein Pseudophase in Normal Saline

Myelin basic protein (MBP), one of the major protein constituents of the myelin sheath, possesses unique ligand-binding features. We present a novel equilibrium headspace gas chromatographic technique to examine the thermodynamics of noncovalent interactions between common perfume components: Lilial, Hedione, Hexylcinnamic aldehyde, and Versalide with MBP monomers and its hexameric MBP-pseudophase. A general theoretical model is used to calculate the critical aggregation concentration (cac) of MBP, perfume component binding constants with monomeric MBP, K11, and MBP as pseudophase, Kn1, and free energies for perfume component binding with monomeric MBP, ΔGb,11, and MBP as pseudophase, ΔGb,n1. In addition, the pseudophase-water partition coefficients, Kx, the free energies of transfer of perfume from bulk water to the MBP-pseudophase, ΔGt, and the intra-aggregate activity coefficients, γm∞, at infinite dilution were also determined. The cac value measured by the method of fractional distribution is a unique and precise approach in understanding the aggregation phenomenon. Within the experimental error, the 1:1 binding free energies did not differ by more than 1 kJ/mol among the perfume components but favored the MBP pseudophase binding by 6 kJ/mol. Therefore, that protein aggregation can enhance the binding of small molecules is probably a general conclusion. While the magnitudes of K11, Kn1, ΔGb, Kx, and ΔGt show weak trends, the γm∞ values show a strong and distinct trend in interaction, spanning 4 orders of magnitude among the perfume components.

Evaluation of cytokines and structural proteins to analyze the pathology of febrile central nervous system disease.

This study was designed to examine the pathophysiological differences in interleukin (IL) and structural protein levels between central nervous system (CNS) disorders associated with heat stroke and CNS stimulants. We measured the concentrations of IL-6, IL-8, neuron-specific enolase (NSE), and myelin basic protein (MBP) in blood and cerebrospinal fluid (CSF) from 87 autopsy cases. In addition, to examine changes in each marker, we cultured nerve cells at 40°C as a heat stroke model and administered 4-aminopyridine and ephedrine in cultured cells as a CNS stimulant model. IL-6 levels in blood and CSF were significantly higher in the stimulant compared with the heat stroke group. IL-8 levels in blood and CSF were relatively high in the stimulant, heat stroke, and psychotropic addiction groups. NSE levels in blood were high in the stimulant and heat stroke groups, while those in CSF were significantly higher in the heat stroke group. MBP levels in blood were markedly higher in the stimulant and heat stroke groups, but no differences were seen in CSF. Compared with the CNS stimulant model, the heat stroke model with cultured human nerve cells showed high values for each marker. The results of the autopsy and laboratory tests in the present cases and those of cultured cell experiments indicated that CNS disorders caused by CNS stimulants such as amphetamines led to changes in IL-6 as an immune response, which suggests that IL-8 may help protect nerve cells in cases involving heat stroke and stimulants.

ASSESSMENT OF THE DEMYELINATING PROCESS ACTIVITY IN PATIENTS WITH HERPESVIRAL MENINGITIS AND MENINGOENCEPHALITIS BASED ON THE LEVEL OF MYELIN BASIC PROTEIN (MBP) IN THE CEREBROSPINAL FLUID

The aim: To study the peculiarities of demyelination by detection of changes in the levels of myelin basic protein (MBP) in CSF of patients with acute herpesviral meningitis (M) and meningoencephalitis (ME). Materials and methods: A total of 136 CSF samples from 68 patients with herpesviral M and ME were collected. The control group consisted of patients with acute respiratory infection and meningismus. MBP level in CSF was identified at the admission and after 10-12 days of treatment. Analysis of MBP concentrations in CSF was performed using an enzyme immunoassay. Results: Examination of patients on the first day of hospitalization showed the presence of a significant increase of MBP in the CSF in all patients with viral M/ME compared with the indicators of the comparison group (р<0.01). In all groups of patients with ME, the level of MBP in CSF was significantly higher than the indicators of comparison group and M groups of the suitable etiology of the disease (p<0.01). In patients with lethal outcome, the MBP level was significantly higher (p<0.01) than in all meningitis groups, but we did not find a significant difference with the patients with ME (p>0.05). Conclusions: The increase of MBP level identified in patients with acute M/ME confirms the presence of the demyelinating process that occurs in all patients, but it is more pronounced in patients with ME.

Feasibility and safety of focused ultrasound-enabled liquid biopsy in the brain of a porcine model

Although blood-based liquid biopsy is a promising noninvasive technique to acquire a comprehensive molecular tumor profile by detecting cancer-specific biomarkers (e.g. DNA, RNA, and proteins), there has been limited progress for brain tumor application partially because the low permeability of the blood-brain barrier (BBB) hinders the release of tumor biomarkers. We previously demonstrated focused ultrasound-enabled liquid biopsy (FUS-LBx) that uses FUS to increase BBB permeability in murine glioblastoma models and thus enhance the release of tumor-specific biomarkers into the bloodstream. The objective of this study was to evaluate the feasibility and safety of FUS-LBx in the normal brain tissue of a porcine model. Increased BBB permeability was confirmed by the significant increase (p = 0.0053) in Ktrans (the transfer coefficient from blood to brain extravascular extracellular space) when comparing the FUS-sonicated brain area with the contralateral non-sonicated area. Meanwhile, there was a significant increase in the blood concentrations of glial fibrillary acidic protein (GFAP, p = 0.0074) and myelin basic protein (MBP, p = 0.0039) after FUS sonication as compared with before FUS. There was no detectable tissue damage by T2*-weighted MRI and histological analysis. Findings from this study suggest that FUS-LBx is a promising technique for noninvasive and localized diagnosis of the molecular profiles of brain diseases with the potential to translate to the clinic.

Mesenchymal Stem Cell Derived Extracellular Vesicles Enhance Myelin Plasticity in Rhesus Monkeys

Cortical injury, such as injury from stroke, results in a cascade of events that includes cell death, inflammation and disruption of myelin. To date, there are no highly effective treatments for reducing the deficits that occur after injury. Recently, we have demonstrated that extracellular vesicles (EVs) harvested from rhesus monkey bone marrow derived cells when given 1 day and 14 days following injury facilitate recovery of function in aged rhesus monkeys within the first 3–5 weeks after cortical injury. Based on these findings and current proteomic literature of MSC‐EVs, we hypothesized that MSC‐EVs enhance myelin plasticity by limiting damage to oligodendrocytes and stimulating remyelination.To assess general myelin integrity after injury, we used Spectral Confocal Reflectance Microscopy (SCoRe) to image myelinated axons and found an increase in the density of myelinated axons in the EV group (p &lt; 0.05). To assess whether the difference was due to reduced damage or remyelination, in sublesional white matter we assessed immunohistochemical labeling of Olig2, a general oligodendrocyte marker, and 8OHdG, a marker for DNA damage. We found reduced densities of Olig2 colocalized with 8OHdG in the EV group (p&lt;0.05). As a marker of active demyelination and myelin debris clearance, we measured Myelin Basic Protein (MBP) concentrations in CSF and found a longitudinal reduction in the EV animals. To assess remyelination, we measured expression of MBP, a gene for myelination in mature oligodendrocytes, Myelin Regulatory Factor (MyRF), a gene for oligodendrocyte differentiation and maintenance, and Breast Carcinoma Amplified Sequence 1 (BCAS1), a gene for newly myelinating oligodendrocytes. Interestingly, we found a 4 fold increase in MyRF expression, and a 1.5 fold increase in MBP and BCAS1 in the EV animals relative to the vehicle control animals in perilesional brain tissue. Consistent with these gene expression differences associated with re‐myelination, we found that the densities of newly‐myelinating oligodendrocytes immune‐labeled with BCAS1, as well as mature oligodendrocytes expressing CC1, exhibited a trend towards an increase in the EV group (p = 0.09). These results suggest that EV treatment reduces myelin damage, while also stimulating myelin repair. Finally, these results correlated with enhanced motor recovery, suggesting that EV‐mediated white matter plasticity is a critical component for recovery after cortical injury.Support or Funding InformationSupported by NIH grant R21NS102991‐02.

MAIT cell subtypes in multiple sclerosis

In patients with multiple sclerosis (MS) and healthy controls (HC) we studied circulating MAIT cells and MAIT cell subtypes expressing CXCR3 and CCR6 by flow cytometry. Absolute numbers of MAIT cells and specifically Tc17-like MAIT cells were lower in patients with primary progressive MS (PPMS) than in controls. Low numbers of Tc17-like MAIT cells were associated with smoking and high concentrations of myelin basic protein in the cerebrospinal fluid. Treatment with alemtuzumab and dimethyl fumarate decreased MAIT cell frequencies. Altogether, we have identified specific MAIT cell subtypes related to PPMS, smoking and demyelination, and MAIT cell effects of MS therapies.

Thermodynamic Analysis of Myelin Basic Protein Adsorbed on Liquid Crystalline Dioleoylphosphatidylcholine Monolayer.

To investigate the stability and dynamic characteristics of monolayer adsorbed on unsaturated lipid dioleoylphosphatidylcholine (DOPC) with varying concentrations of myelin basic protein (MBP), the system is studied by applying Langmuir technique and making atomic force microscope (AFM) observation, which is based on the mass conservation equation analysis method referred to in the thermodynamics theory. As indicated by surface pressure-mean molecular area (π − A) and surface pressure-adsorption time (π − T) isotherms, the physical properties of monolayer derived from the interaction of varying concentrations of MBP with liquid crystalline unsaturated lipid DOPC molecules were qualitatively studied. As revealed by surface morphology analysis with AFM, the micro region was expanded as the concentration of MBP in the subphase was on the increase, suggesting that hydrophobic interactions led to the MBP insertion, thus causing accumulation of the MBP on the surface of the monolayer. Experimental results have demonstrated that the partition coefficient of the interaction between MBP and unsaturated phospholipid DOPC and the molecular area of MBP adsorbed on the monolayer film was calculated using the mass conservation equation. In addition, not only does the varying concentration of MBP in the subphase exerts significant effects on the arrangement and conformation of DOPC monolayer, it also has certain guiding significance to exploring the structural changes to biofilm supramolecular aggregates as well as the pathogenesis and treatment of related diseases.

Vitamin D and neurospecific proteins in children with inflammatory demyelinating diseases of central nervous system

The relevance of studying the provision of vitamin D in children with inflammatory diseases of the central nervous system (CNS) is due to a high prevalence of vitamin D deficiency conditions in children population, which, according to current literature data, leads to the imbalance of the immune system and a predisposition to a severe disease course, chronization of the process, development of autoimmune pathology. The study of the concentration of neurospecific proteins (NSP) in blood serum and cerebrospinal fluid (CSF) has been recently used to analyze the degree and nature of nervous tissue damage in case of various CNS diseases. The study included investigation of blood serum and CSF samples obtained from 107 children (34 – with encephalitis, 28 – with disseminated encephalomyelitis (DEM), 20 – with multiple sclerosis (MS), 25 – control group). Determination of vitamin D levels (25(OH)D) was performed by the method of electrochemiluminescence immunoassay, concentrations of myelin basic protein, neuron-specific enolase, S100 protein and glial fibrillary acidic protein – by ELISA method. A decrease in the concentration of vitamin D under 30 ng/ml was found in 95% of children with inflammatory diseases of the central nervous system, while the severity of the deficiency of 25(OH)D was associated with the severity of the disease course. In the early stages of the disease in all groups, a significant increase in the level of the main myelin protein was found, while an increase in the concentration of other NSP was observed less frequently and was associated with a severe and complicated course of the disease. Correlations of different intensity and direction between NSP and 25(OH)D were found, which indicates their importance in the pathogenesis of inflammatory diseases of CNS.

Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines.

Severe Traumatic Brain Injury in Infants, Children, and Adolescents in 2019: Some Overdue Progress, Many Remaining Questions, and Exciting Ongoing Work in the Field of Traumatic Brain Injury ResearchIn this Supplement to Pediatric Critical Care Medicine, we are pleased to present the Third Edition o

Diagnostic significance of the determination of myelin basic protein in cerebrospinal fluid in HIV-associated neurological diseases.

48 patients aged from 21 to 54 years, infected with human immunodeficiency virus (HIV) and presence of diseases of the central nervous system (CNS) were examined. CNS diseases included cerebral tuberculosis, viral encephalitis (caused by Epstein-Barr Virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV)), encephalitis of unspecified etiology, cerebral toxoplasmosis, fungal meningitis. 29 (60.4%) of the patients were discharged from the hospital with a clinical improvement, and 19 (39.6%) of the patients died as a result of CNS disease. Significant differences in the content of the myelin basic protein (MBP) in the cerebrospinal fluid (CSF), depending on the outcome of the disease, were determined. The Median of MBP in deceased patients was 2.9 times higher than in the survived patients - 4.00 (1.90-7.70) ng/ml vs. 1.40 (0.99-2.00) ng/ml (p=0.002 U). An inverse correlation between the content of MBP in the CSF and the time from the determination of the HIV status to the manifestation of neurologic symptoms (rs=-0.30, p&lt;0.05) was found. According to the results of the ROC analysis, the high risk of unfavorable course of HIV-associated CNS diseases is predicted when the concentration of MBP in the cerebrospinal fluid increases by more than 2 ng/ml (68.4% sensitivity, 75.9% specificity, 72.9% accuracy). The highest level of this protein was observed in patients with fungal lesions of the central nervous system (6.6 (1.9-7.8) ng/ml), and the lowest MBP level – in the group of patients with unspecified encephalitis (0.99 (0.9-1.1) ng/ml), which correlated to more favorable outcomes of the disease. The MBP in cerebrospinal fluid can be an important diagnostic and prognostic marker of HIV-associated neurological diseases.

Defining active progressive multiple sclerosis

Background: It is unknown whether disease activity according to consensus criteria (magnetic resonance imaging activity or clinical relapses) associate with cerebrospinal fluid (CSF) changes in progressive multiple sclerosis (MS). Objective: To compare CSF biomarkers in active and inactive progressive MS according to consensus criteria. Methods: Neurofilament light chain (NFL), myelin basic protein (MBP), IgG-index, chitinase-3-like-1 (CHI3L1), matrix metalloproteinase-9 (MMP-9), chemokine CXCL13, terminal complement complex, leukocyte counts and nitric oxide metabolites were measured in primary (n = 26) and secondary progressive MS (n = 26) and healthy controls (n = 24). Results: Progressive MS patients had higher CSF cell counts, IgG-index, CHI3L1, MMP-9, CXCL13, NFL and MBP concentrations. Active patients were younger and had higher NFL, CXCL13 and MMP-9 concentrations than inactive patients. Patients with active disease according to consensus criteria or detectable CXCL13 or MMP-9 in CSF were defined as having combined active progressive MS. These patients had increased CSF cell counts, IgG-index and MBP, NFL and CHI3L1 concentrations. Combined inactive patients only had increased IgG-index and MBP concentrations. Conclusion: Patients with combined active progressive MS show evidence of inflammation, demyelination and neuronal/axonal damage, whereas the remaining patients mainly show evidence of active demyelination. This challenges the idea that neurodegeneration independent of inflammation is crucial in disease progression.

Patient controlled epidural analgesia with dexmedetomidine during cesarean section did not impair somatosensory evoked potentials and serum myelin basic protein

Objective To investigate whether patient controlled epidural analgesia(PCEA) with dexmedetomidine(Dex) during cesarean section has no effect on somatosensory evoked potential(SEP) upon lower limb stimulation and serum myelin basic protein(MBP). Methods A total of one hundred and twenty puerperants receiving cesarean section were randomly divided into three groups (n=40): group R received 0.1% ropivacaine only, group RM received 0.002%morphine+0.1% ropivacaine, group RD received 2 μg/kg Dex+0.1% ropivacaine. VAS score, observer's assessment of alertness/sedation(OAA/S) score, HR, MAP were examined 2 h(T1), 4 h(T2),8 h(T3),12 h(T4), 24 h(T5) and 48 h(T6) after surgery. SEPs and concentrations of serum MBP were tested before and after surgery. Adverse effects were also assessed. Results VAS scores at T3, T4, T5 of group RM (1.8±0.8, 1.8±0.8, 1.9±0.9) and RD (1.7±0.6, 1.9±0.7, 1.9±0.5) were lower than those of group R (2.1±0.6, 2.3±0.6, 2.3±0.6)(P 0.05). Satisfaction rates of analgesia and OAA/S scores had no significant difference among three groups (P>0.05). Incidence of nausea, dizziness and pruritus of group RM (32%, 15%, 18%) were higher than those of group R (12%, 0, 0) and group RD (12%, 2%, 2%)(P 0.05). Conclusions Dex 2 μg/kg used for PCEA after cesarean section did not affect serum MBP and SEP, therefore, is a safe analgesic with minimal adverse effect. Key words: Dexmedetomidine; Patient controlld epidural analgesia; Somatosensory evoked potential; Myelin basic protein