S100B in underweight and weight-recovered patients with anorexia nervosa

Anorexia nervosa (AN) commonly arises during adolescence, leading to interruptions of somatic and psychological development as well as to cortical atrophy and reductions of brain volume. While most brain changes shift towards normal with weight restoration, it is not certain whether they are related to the loss of brain cells, neuropil or merely due to fluid shifts. We measured S100B serum concentrations and psychometric characteristics in 34 patients with acute AN, 19 weight-recovered patients and 35 healthy control women (HCW). Plasma tryptophan and leptin levels were determined as markers for malnutrition and neuroendocrine adaptation to semi-starvation. Peripheral S100B concentrations of acute and former AN patients were not elevated and not statistically different from HCW. BMI, peripheral leptin levels and measures of psychopathology as well as executive cognitive functioning did not correlate with S100B. Plasma tryptophan was positively related to S100B. Our results are in line with our previous findings showing unaltered GFAP and NSE plasma levels in patients with acute AN. Together they do not support hypotheses comprising the degeneration of glial or neuronal cells to explain common signs of brain atrophy in patients with acute AN.     

Increased GFAP and S100β but not NSE serum levels after subarachnoid haemorrhage are associated with clinical severity

Assessment of initial disease severity after subarachnoid haemorrhage (SAH) remains difficult. The objective of the study is to identify biochemical markers of brain damage in peripheral blood after SAH. Hospital admission S100beta, glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) serum levels were analysed in 67 patients with SAH. Disease severity was determined by using the World Federation of Neurological Surgeons (WFNS) scale and the Fisher CT (computerized tomography) grading scale. Mean astroglial serum concentrations taken at hospital admission were increased (S100beta 2.8-fold and GFAP 1.8-fold) compared with the upper limit of normal laboratory reference values (P95). The mean NSE concentration was within normal limits. S100beta (P < 0.001) and GFAP (P =0.011) but not NSE levels were higher in patients who were in coma at the time of hospital admission compared with patients who were not. Similarly S100beta and GFAP but not NSE serum levels increased with higher WFNS scores, raised intracranial pressure and higher CT Fisher grade scores. Concerning the location of the aneurysm, S100beta and GFAP serum levels were within normal limits after a perimesencephalic type of haemorrhage and significantly increased after aneurysmal type SAH. Increased glial (S100beta and GFAP) but not neuronal (NSE) protein serum concentrations are found after SAH, associated to the clinical severity of the initial injury.     

颅脑损伤患者血清GFAP和NSE的变化与神经功能缺损程度的相关性研究

目的探讨颅脑损伤患者血清胶质纤维酸性蛋白（GFAP）和神经元特异性烯醇化酶（NSE）的水平变化,并根据预后美国国立卫生院神经功能缺损评估量表（NIHSS）进行相关性分析。 方法选取北京市红十字会急诊抢救中心神经外科自2017年4月至2018年3月收治的颅脑损伤患者140例,根据NIHSS评分将患者分为对照组（20例,NIHSS 0~1分）、轻度组（40例,NIHSS 2~15分）、中度组（40例,NIHSS 16~20分）及重度组（40例,NIHSS 21~42分）,对症治疗并通过酶联免疫吸附法进行GFAP和NSE不同时间点的动态检测。比较不同损伤水平患者两个指标的变化趋势,分析两个指标与NIHSS水平的相关性。 结果轻、中、重度组患者血清GFAP和NSE水平显著高于对照组,差异具有统计学意义（P<0.05）。轻、中、重度组间不同时间段GFAP及NSE水平变化比较,差异有统计学意义（P<0.05）,且重度组GFAP、NSE浓度显著增高。患者血清GFAP和NSE水平与NHISS评分均呈正相关（r=0.484,0.447,P<0.05）。 结论颅脑损伤患者血清GFAP和NSE水平和神经功能缺损程度密切相关,动态监测有助于评估患者病情演变和神经功能缺损的严重程度。     

脑出血患者血清NSE、GFAP、BDNF水平变化与认知障碍相关性研究

目的探讨脑出血患者血清神经元特异性烯醇化酶(NSE)、胶质纤维酸性蛋白(GFAP)、脑源性神经营养因子(BDNF)水平变化与认知障碍相关性。方法选择急性自发性脑出血患者100例,入院时均给予相应治疗,并进行NSE、GFAP、BDNF检测。将100例患者依据是否发生认知障碍分为认知障碍组(57例)和无认知障碍组(43例)。并比较不同损伤水平(MMSE评分)患者三个指标之间的差异、计算三个指标与MMSE水平的相关性。结果认知功能障碍组患者血清NSE、GFAP水平均显著高于无认知功能障碍组,BDNF显著低于无认知功能障碍组(t=7.039,t=2.247,t=4.847,P0.01)。轻度损伤组、中度损伤组和重度损伤组间血清NSE、GFAP、BDNF水平存在显著差异(F=22.752,F=31.506,F=38.294,P0.01)。血清NSE、GFAP水平与MMSE评分正相关(r=0.641,r=0.604,P0.05),BDNF与MMSE评分负相关(r=0.582,P0.05)。结论脑出血患者血清NSE、GFAP、BDNF水平与脑出血患者卒中后认知功能障碍密切相关,可用于判断脑出血患者认知功能障碍的严重程度。     

The role of leptin and cortisol in hyperactivity in patients with acute and weight-recovered anorexia nervosa

Introduction

In food-restricted rats, leptin as well as corticotropin releasing factor attenuate semistarvation-induced hyperactivity (SIH). Results from studies in patients with anorexia nervosa (AN) showed an association between excessive physical activity (PA) and leptin. One recent report suggests a role for cortisol in PA. In this study, we assessed the relationships between PA and both, cortisol and leptin levels at the same time in patients with acute anorexia nervosa (acAN) in comparison to recovered patients (recAN).

Methods

Plasma leptin, plasma cortisol, body mass index (BMI), and expert-ratings of qualities of PA were assessed in 36 acAN patients, 27 recAN patients and 44 healthy control woman (HCW). Regression analyses were used to predict PA using BMI, leptin and cortisol levels as predictor variables.

Results

Leptin levels but not cortisol significantly contributed to the prediction of PA in acAN. In recAN PA was not elevated and not related to endocrine parameters but correlated positively with core eating disorder symptoms.

Conclusions

Our work lends support to the proposed inverse association between peripheral leptin levels and excessive physical activity in AN. This relationship is specific to the state of semistarvation. The role of additional mediators remains to be clarified.     

Analysis of cerebrospinal fluid glial fibrillary acidic protein after seizures in children

PURPOSE: To evaluate pediatric seizure patients for astrocytic injury by measuring cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP), determine risk factors for GFAP elevation after seizures, and compare seizure-induced astrocyte injury with neuronal injury by concurrent measurement of CSF neuron-specific enolase (NSE). METHODS: CSF obtained from pediatric patients (n = 52) within 24 h of seizure was assayed for GFAP and NSE. Retrospective chart review was performed for seizure type, duration, and etiology. RESULTS: Overall, children with seizures had elevated CSF GFAP compared with controls (p = 0.0075), but no elevation of NSE (p = 0.1437). No effect of seizure type or etiology was found, but a significant positive effect of seizure duration (p = 0.0010) and status epilepticus (p = 0.0296) was seen on CSF GFAP. Individually, seven children (13%) had elevated GFAP (>440 pg/ml); in five children, the increased GFAP was not accompanied by elevations in NSE (<12 ng/ml). Five children with elevated GFAP had symptomatic etiologies for their seizures, but the etiology of one child with elevated GFAP was cryptogenic, and one had febrile seizures. CONCLUSIONS: Elevation of CSF GFAP after seizures suggests that astrocytic injury may occur in a subgroup of children, primarily in the context of prolonged seizures and symptomatic etiologies. Increased GFAP levels may occur in patients with normal NSE, suggesting that GFAP may be a more sensitive marker of brain injury in some cases.     

The 5-HTTLPR polymorphism, platelet serotonin transporter activity and platelet serotonin content in underweight and weight-recovered females with anorexia nervosa

Serotonin (5-HT) pathways play an important role in the pathophysiology of anorexia nervosa (AN). In this study, we investigated functional characteristics of the platelet 5-HT transporter and platelet 5-HT content in AN patients at various stages of their illness in comparison to healthy control woman (HCW) controlling for the 5-HTTLPR deletion/insertion polymorphism and other confounding variables. Fasting blood samples of 58 acutely underweight AN patients (acAN, BMI = 15.2 ± 1.4), 26 AN patients of the initial acAN sample after short-term/partial weight restoration (BMI = 17.3 ± 0.9), 36 weight-recovered AN patients (recAN, BMI = 20.7 ± 2.2) and 58 HCW (BMI = 21.6 ± 2.0) were assessed for kinetic characteristics of platelet 5-HT uptake (V _max, K _m) and platelet 5-HT content. Plasma leptin served as an indicator of malnutrition. Mean V _max and K _m values were significantly higher in recAN subjects in comparison to HCW (2.05 ± 0.62 vs. 1.66 ± 0.40 nmol 5-HT/10⁹ platelets min and 432 ± 215 vs. 315 ± 136 nmol, respectively) but there were no differences in platelet 5-HT content (464.8 ± 210.6 vs. 472.0 ± 162.2 ng 5-HT/10⁹ platelets). 5-HT parameters in acAN patients and HCW were similar. 5-HTTLPR variants were not related to 5-HT platelet variables. In the longitudinal part of the study we found significantly increased 5-HT content but unchanged 5-HT uptake in AN patients after short-term/partial weight restoration. Our results highlight the importance of malnutrition for the interpretation of abnormalities in neurotransmitter systems in AN. Changes in platelet 5-HT transporter activity were related to the stage of the illness but not to 5-HTTLPR genotype. Increased V _max and K _m in recovered AN patients might mirror adaptive modulations of the 5-HT system.     

Explorative investigation of biomarkers of brain damage and coagulation system activation in clinical stroke differentiation

Introduction   A simple and accurate method of differentiating ischemic stroke and intracerebral hemorrhage (ICH) is potentially useful to facilitate acute therapeutic management. Blood measurements of biomarkers of brain damage and activation of the coagulation system may potentially serve as novel diagnostic tools for stroke subtypes. Methods   Ninety-seven stroke patients were prospectively investigated in a multicenter design with blood levels of brain biomarkers S100B, neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP) as well as a coagulation biomarker, activated protein C – protein C inhibitor complex (APC-PCI), within 24 hours of symptom onset. Results   Eighty-three patients (86 %) had ischemic stroke and fourteen patients (14 %) had ICH. There were no differences in S100B (p = 0.13) and NSE (p = 0.67) levels between patients with ischemic stroke or ICH. However, GFAP levels were significantly higher in ICH patients (p = 0.0057). APC-PCI levels were higher in larger ischemic strokes (p = 0.020). The combination of GFAP and APC-PCI levels, in patients with NIHSS score more than 3, had a sensitivity and negative predictive value of 100 % for ICH in our material (p = 0.0052). Conclusion   This exploratory study indicated that blood levels of biomarkers GFAP and APC-PCI, prior to neuroimaging, may rule out ICH in a mixed stroke population.     

Reduced astrocyte density underlying brain volume reduction in activity-based anorexia rats

Objectives: Severe grey and white matter volume reductions were found in patients with anorexia nervosa (AN) that were linked to neuropsychological deficits while their underlying pathophysiology remains unclear. For the first time, we analysed the cellular basis of brain volume changes in an animal model (activity-based anorexia, ABA).

Methods: Female rats had 24?h/day running wheel access and received reduced food intake until a 25% weight reduction was reached and maintained for 2 weeks.

Results: In ABA rats, the volumes of the cerebral cortex and corpus callosum were significantly reduced compared to controls by 6% and 9%, respectively. The number of GFAP-positive astrocytes in these regions decreased by 39% and 23%, total astrocyte-covered area by 83% and 63%. In neurons no changes were observed. The findings were complemented by a 60% and 49% reduction in astrocyte (GFAP) mRNA expression.

Conclusions: Volumetric brain changes in ABA animals mirror those in human AN patients. These alterations are associated with a reduction of GFAP-positive astrocytes as well as GFAP expression. Reduced astrocyte functioning could help explain neuronal dysfunctions leading to symptoms of rigidity and impaired learning. Astrocyte loss could constitute a new research target for understanding and treating semi-starvation and AN.     

The impact of hyperactivity and leptin on recovery from anorexia nervosa

Summary In anorexia nervosa (AN), hyperactivity is observed in about 80% of patients and has been associated with low leptin levels in the acute stage of AN and in anorexia animal models. To further understand the importance of this correlation in AN, we investigated the relationship between hypoleptinaemia and hyperactivity in AN patients longitudinally and assessed their predictive value for recovery. Body weight, activity levels, and serum leptin levels were assessed in adolescents and adult AN patient groups at the start and during treatment, up to a year. In the adolescent group, initial leptin and activity levels were correlated. This negative correlation changes over time into a positive correlation with physiological recovery. Treatment outcome in both groups could be predicted by initial BMI and leptin levels but not by activity levels. No major relationship of activity with the course of recovery was detected, suggesting that in contrast to the acute stage of the disease, leptin and activity levels during the recovery process are dissociated.     

Circulating leptin in patients with anorexia nervosa, bulimia nervosa or binge-eating disorder: relationship to body weight, eating patterns, psychopathology and endocrine changes

A decreased production of leptin has been reported in women with anorexia nervosa (AN) and has been attributed merely to the patients' reduced body fat mass. The extent to which eating patterns, purging behaviors, psychopathology and endocrine changes may contribute to the genesis of leptin alterations has not been deeply investigated. Therefore, we measured plasma levels of leptin, glucose and other hormones in three groups of eating disorder patients with different body weight (BW), eating patterns and purging behaviors. Sixty-seven women, 21 with AN, 32 with bulimia nervosa (BN), 14 with binge-eating disorder (BED) and 25 healthy females volunteered for the study. We found that circulating leptin was significantly reduced in AN and BN patients, but significantly enhanced in women with BED. In anorexics, plasma glucose was decreased, whereas plasma cortisol was enhanced; blood concentrations of 17beta-estradiol and prolactin (PRL) were reduced in both AN, BN and BED patients. In all subject groups, a strong positive correlation emerged between plasma levels of leptin and the subjects' BW or body mass index, but not between leptin and psychopathological measures, plasma glucose, cortisol, PRL and 17beta-estradiol. Since leptin was reduced in both underweight anorexics and normal weight bulimics, but increased in overweight BED women, who compulsively binge without engaging in compensatory behaviors, we suggest that factors other than BW may play a role in the determination of leptin changes in eating disorders.     

Elevated Serum Glial Fibrillary Acidic Protein (GFAP) is Associated with Poor Functional Outcome After Cardiopulmonary Resuscitation

Background

The neurological prognosis of patients after cardiopulmonary resuscitation (CPR) is difficult to assess. GFAP is an astrocytic intermediate filament protein released into bloodstream in case of cell death. We performed a prospective study aiming to compare the predictive potential of GFAP after resuscitation to the more widely used biomarker neuron-specific enolase (NSE).

Methods

One hundred patients were included at 48 h (tolerance interval ±12 h) after cardiac arrest. A serum sample was collected immediately after study inclusion. We determined serum levels of GFAP and NSE by means of immunoassays. Primary outcome was the modified Glasgow outcome scale at 4 weeks. Values below four were considered as a poor functional outcome.

Results

Median GFAP levels in poor outcome (n = 61) and good outcome (n = 39) patients were 0.03 μg/L (interquartile range 0.01–0.07 μg/L) and 0.02 μg/L (0.01–0.03 μg/L; p = 0.014), respectively. GFAP revealed a sensitivity of 60.7% and a specificity of 66.7% to predict a poor functional outcome. All patients having a GFAP level >0.08 µg/L had a poor functional outcome. For NSE, sensitivity was 44.3% and specificity was 100.0% for predicting a poor outcome. Multivariate regression analysis revealed GFAP, NSE, and the Karnofsky index to be independent predictors of outcome.

Conclusions

The release patterns of GFAP and NSE after CPR show differences. GFAP levels above 0.08 µg/L were associated with a poor outcome in all cases, and patients with strongly elevated values (>3 µg/L) consistently had severe brain damage on brain imaging. Both biomarkers independently contribute to outcome prediction after CPR.

     

Studies of the brain specificity of S100B and neuron-specific enolase (NSE) in blood serum of acute care patients

Laboratory monitoring with damage markers of brain and of non-nervous tissues in blood serum of 401 acute care patients showed increased contents of neuron-specific enolase (NSE) and S100B besides raised levels of markers of heart, skeletal muscle, bile duct, liver, prostate, kidney, salivary gland damage or of inflammatory stress to varying frequencies. Correlation between raised NSE and S100B contents ascertained brain damage. Correlation between raised NSE and troponin I (cTnI) values indicated brain damage induced by heart failure (probably caused by hypoxia and anemia); this was assessed with correlations between NSE and other heart markers, e.g. creatine kinase (CK) isoenzymes, alpha-hydroxybutyrate dehydrogenase. S100B did not show such correlations: data indicated S100B release from non-nervous tissues having high S100B content, e.g. fat, cartilage, skin. S100B release might be triggered by inflammatory stress and tissue damage. This was further supported by low NSE/S100B concentration ratios in serum compared to cerebrospinal fluid (CSF) of patients with comatose state, convulsive status, or intracerebral hemorrhage. Our data revealed CSF to be the relevant sample to monitor brain damage with NSE and S100B, whereas in serum raised S100B levels together with normal NSE levels indicated release from non-nervous tissues of acute care patients pointing out multi-organ dysfunction.     

脑红蛋白在大鼠脑内表达的细胞定位

目的研究脑红蛋白(NGB)在正常大鼠脑内表达的细胞定位。方法常规方法制备SD大鼠脑组织冰冻切片。以神经元特异性烯醇化酶(NSE)和胶质纤维酸蛋白(GFAP)作为对照,分别与NGB进行免疫荧光双标记染色,共聚焦显微镜照相分析。结果免疫荧光双标和图像分析的结果表明,NGB在大鼠脑内表达的细胞定位与NSE相同,存在于神经元的胞浆中。NGB与GFAP表达的细胞不同。结论NGB在正常大鼠脑内神经元中表达,提示与脑神经元的功能活动密切相关。     

The role of leptin in anorexia nervosa: clinical implications

Leptin is a hormone with pleiotropic functions affecting several tissues. Because leptin has a crucial role in the adaptation of an organism to semi-starvation, anorexia nervosa (AN) serves as a model disorder to elucidate the functional implications of hypoleptinaemia; vice versa, several symptoms in patients with this eating disorder are related to the low leptin levels, which are characteristic of acute AN. Weight gain in AN patients can induce relative hyperleptinaemia in comparison to controls matched for body mass index; circulating leptin concentrations in AN patients thus transverse from subnormal to supranormal levels within a few weeks. We review findings on leptin secretion in AN and focus on implications, particularly for the hypothalamus-pituitary-gonadal axis, bone mineral density and physical hyperactivity. Undoubtedly, the elucidation of leptin's function as a trigger of diverse neuroendocrine adaptations to a restricted energy intake has substantially advanced our knowledge of the pathogenesis of distinct symptoms of AN, including amenorrhoea that represents one of the four diagnostic criteria. The fact that hypoleptinaemia can induce hyperactivity in a rat model for AN has led to a series of studies in AN patients, which support the notion that application of leptin to severely hyperactive patients might prove beneficial.     

Screening for anorexia nervosa via measurement of serum leptin levels

Due to their sub-normally low fat mass, leptin levels in patients with acute anorexia nervosa (AN) are well below reference levels for age and sex-matched controls. This hypoleptinemia entails endocrinological and behavioral characteristics observed in AN patients during starvation. We aimed to study the appropriateness of hypoleptinemia as a diagnostic marker for AN by assessing sensitivity, specificity and likelihood ratios for different referral serum leptin levels for predicting anorexia nervosa and healthy leanness. For prediction, we additionally generated a score based on a multivariate logistic model including body mass index (BMI; kg/m2) and leptin level. For this purpose, we measured leptin levels in 74 female patients with acute AN upon admission for inpatient or outpatient treatment. Adolescent and adult patients were recruited according to DSM-IV criteria from two multi-center studies. Additionally, leptin levels were measured in 65 female healthy, lean students. Mean serum leptin level was significantly decreased in patients with AN compared to underweight controls (0.87?±?0.90 vs. 6.43?±?3.55?μg/L, p?相似文献   

Cerebrospinal Fluid and Serum Neuron-Specific Enolase Levels After Febrile Seizures

PURPOSE: Neuron-specific enolase (NSE) has been established as a reliable marker of neuronal damage in various neurologic disorders. The aim of this study was to evaluate whether febrile seizures (FS) cause brain damage, based on the serum and cerebrospinal fluid (CSF) levels of NSE. METHODS: Fifty-three patients aged from 6 months to 7 years were enrolled. Among them, 36 patients had generalized seizures, and 17 had partial seizures. The maximal seizure duration was 90 min. Blood and CSF samples for measurement of NSE were obtained immediately after the seizure. NSE was measured using an enzyme immunoassay (EIA). RESULTS: Serum and CSF levels of NSE ranged up to 10 ng/mL, but very high levels were not observed. In patients with partial seizures, the NSE level in the CSF and the ratio of the CSF to serum NSE levels showed a strong correlation with seizure duration. Conversely, there were no correlations between NSE levels and seizure duration in the patients with generalized seizures. CONCLUSIONS: These results indicate that FS seldom cause severe neurologic damage, but prolonged partial seizures may cause slight neuronal injury.     

肺炎链球菌溶血素致脑损伤中细胞凋亡及凋亡诱导因子的变化及意义

目的 探讨肺炎链球菌溶血素(PLY)致感染性脑损伤中细胞凋亡及凋亡诱导因子(AIF)的表达及意义. 方法 SD大鼠80只按随机数字表法分为PLY组[颈内动脉注射0.2 mL(7μg) PLY]和生理盐水(NS)组(颈内动脉注射等体积NS),每组40只.每组按观察时间点分为6h、12h、24 h、48 h4个亚组,每亚组10只,其中5只注射髓,甲酰胺法测定脑组织EB含量判断血脑屏障(BBB)的破坏程度.5只不注射EB,取脑组织切片,应用免疫组化和TUNEL染色分别检测脑组织神经元特异性烯醇化酶(NSE)、胶质纤维酸性蛋白(GFAP)、AIF蛋白含量和细胞凋亡. 结果 与NS组比较,造模后各时间点PLY组大鼠脑组织EB、NSE、GFAP、AIF蛋白含量均较高,细胞凋亡较多,差异均有统计学意义(P＜0.05); PLY组大鼠脑组织凋亡细胞数与AIF蛋白的表达呈正相关关系(r=0.959,P=0.000). 结论 细胞凋亡参与了PLY诱导的脑损伤的发展过程,AIF可能介导了神经细胞的凋亡.     

颞叶癫(癎)大鼠(癎)性发作后神经元特异性烯醇化酶、髓鞘碱性蛋白的变化及其意义

目的观察神经元特异性烯醇化酶(NSE)、髓鞘碱性蛋白(MBP)在海人酸(KA)颞叶癫癎大鼠癎性发作后各时间点血液中的动态变化,探讨颞叶癫癎发作后脑神经元和神经髓鞘损伤程度。方法KA注射大鼠海马部位建立颞叶癫癎模型,在癎性发作后3h、6h、12h、24h、48h、72h抽取血液,测定其血清中NSE、MBP含量。结果癫癎发作后NSE和MBP含量逐渐增高,24hNSE含量最高,72hMBP含量最高。结论癫癎发作后存在神经元损伤和坏死,继之出现脑白质神经髓鞘损伤。