Neuron-specific Enolase Protein Research Articles

Evaluation of Cognitive and Biochemical Brain Status in Patients after Carotid Endarterectomy

INTRODUCTION: In the large studies such as NASCET, ESCT, VACS, ACAS and ACST-1, the role of alteration of the cognitive functions of a patient in the early and long-term postoperative periods have not been determined.
 AIM: To evaluate the biochemical parameters of cerebral functions, the cognitive status of patients, and their interrelation after carotid endarterectomy.
 MATERIALS AND METHODS: The study involved 60 patients divided into two groups. The mean age was 67.3 ± 7.9 years, there were 49 (81%) men and 19 (19%) women. Group A included ‘symptomatic’ patients (n = 30) who underwent carotid endarterectomy and had a history of an acute cerebrovascular event. Group B included ‘asymptomatic’ patients (n = 30) who underwent carotid endarterectomy but had no history of cerebrovascular events. As part of the study, the following data were evaluated within a 6-month period: cognitive status (on MMSE, FAB, MoCA-test, NIHSS scales), biochemical parameters (S100b protein, neuron specific enolase (NSE), brain derived neurotrophic growth factor (BDNF)) and the ultrasound data of the carotid arteries.
 RESULTS: Patients of group A showed improvement of the cognitive status by the 6th month on MMSE scale (p = 0.001) and in MoCA-test (p = 0.09) relative to the initial parameters; on FAB scale relative to the data after 1 month (p = 0.01); a decline of the level of neurological deficit on NIHSS scale (p = 0.01). In group A, an inverse correlation was found between the results on MMSE scale and resistance index (r = -0.675; p = 0.005), and a direct correlation between the results on FAB scale and the end diastolic pressure in the internal carotid artery (r = +0.912; p = 0.005) according to the ultrasound data. The data obtained in group B, reflected improvement of the cognitive status by the 6th month only by 2 points on MoCA test (p = 0. 03) relative to the initial data. Besides, in 6 months after the surgery, there was a 2-fold increase in S100b marker (p = 0.01) and NSE protein (p = 0.02) and a 1.5-fold increase in BDNF protein as compared to the initial values (p = 0.005).
 CONCLUSIONS: Carotid endarterectomy leads to improvement of the cognitive status evaluated on MMSE, FAB, MoCA, NIHSS scales in the long-term postoperative period in symptomatic patients. The extent of improvement of neuropsychological status depends on the level of the end diastolic pressure and resistance index in the internal carotid artery on the operated side.

Neuroinflammation Process as a Key Etiopathogenetic Factor in the Evolution of Autism Spectrum Disorders in Child Patients

Background: the prevalence of autism spectrum disorders (ASD) is increasing every year, however, diagnostic and therapeutic options are still limited. Aim: identification the patterns of the neuroinflammation process in the etiopathogenesis of ASD of child patients. Patients and methods: clinical, anamnestic and laboratory data of 85 child patients with a confirmed ASD diagnosis. Each patient was assessed for the level of neurospecific proteins (neuron-specific enolase (NSE), S100b protein), the indices of the “Neuro-immuno-test” panel (leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) activity, autoantibodies to S100b protein and myelin basic protein) in the blood before and after a standardized three-month-course of treatment. The reference interval of the laboratory was taken as normal values. The clinical picture was assessed according to the Childhood Autism Rating Scale (CARS). The correlation calculations were carried out in the MS Excel program. Results: in this work we describe the dynamics of the neuroinflammation process parameters in children with autism-like syndrome and psycho-speech development delay on the basis of complex anti-inflammatory therapy. The results of the research prove the increase in NSE and S100b protein quantity among 85% of patients before the treatment. More than 60% of patients had the increase of the parameters of the Neuro-test panel. The severity levels of symptoms among patients according to the scales used specified moderate and severe autism. The quantity of neurospecific proteins and immunological parameters correlated with CARS scale scores. Positive dynamics of clinical symptoms and studied parameters decrease were observed while therapy. The use of the parameters allows to evaluate objectively the severity levels of the patient’s immunomitochondrial status and shows a congruent change on the basis of etiopathogenetic therapy.

[Effect of Wnt/β-catenin signaling pathway in neural differentiation of human bone marrow mesenchymal stem cells].

To explore the effect of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and the combination of bFGF and EGF in the neural differentiation of human bone marrow mesenchymal stem cells (hBMSCs), and the role of Wnt/β-catenin signaling pathway in this process. The identified 4th-generation hBMSCs were divided into five groups according to different induction conditions, namely control group (group A), EGF induction group (group B), bFGF induction group (group C), EGF and bFGF combined induction group (group D), and EGF, bFGF, and Dickkopf-related protein 1 (DKK-1) combined induction group (group E). After 7 days of continuous induction, the cell morphology was observed by inverted fluorescence phase contrast microscopy, levels of genes that were related to neural cells [Nestin, neuron-specific enolase (NSE), microtubule-associated protein 2 (MAP-2), and glial fibrillary acidic protein (GFAP)] and key components of the Wnt/β-catenin signaling pathway (β-catenin and Cyclin D1) were detected by RT-PCR, and the levels of proteins that were related to neural cells (Nestin and GFAP) as well as genes that were involved in Wnt/β-catenin signaling pathway [β-catenin, phosphorylation β-catenin (P-β-catenin), Cytoplasmic β-catenin, and Nuclear β-catenin] were explored by cellular immunofluorescence staining and Western blot. When compared to groups A and B, the typical neuro-like cell changes were observed in groups C-E, and most obviously in group D. RT-PCR showed that the relative expressions of Nestin, NSE, and MAP-2 genes in groups C-E, the relative expressions of GFAP gene in groups D and E, the relative expression of NSE gene in group B, the relative expressions of β-catenin gene in groups C and D, and the relative expressions of Cyclin D1 gene in groups B-D significantly increased when compared with group A ( P<0.05). Compared with group E, the relative expressions of Nestin, NSE, MAP-2, GFAP, β-catenin, and CyclinD1 genes significantly increased in group D ( P<0.05); compared with group C, the relative expression of Nestin gene in group D significantly decreased ( P<0.05), while NSE, MAP-2, and GFAP genes significantly increased ( P<0.05). The cellular immunofluorescence staining showed that the ratio of NSE- and GFAP-positive cells significantly increased in groups C-E than in group A, in group D than in groups C and E ( P<0.05). Western blot assay showed that the relative expression of NSE protein was significantly higher in groups C and D than in group A and in group D than in groups C and E ( P<0.05). In addition, the relative expression of GFAP protein was significantly higher in groups C-E than in group A and in group D than in group E ( P<0.05). Besides, the relative expressions of β-catenin, Cytoplasmic β-catenin, Nuclear β-catenin, and the ratio of Nuclear β-catenin to Cytoplasmic β-catenin were significantly higher in groups C and D than in group A and in group D than in group E ( P<0.05), whereas the relative expression of P-β-catenin protein was significantly lower in groups C and D than in group A and in group D than in group E ( P<0.05). Different from EGF, bFGF can induce neural differentiation of hBMSCs. In addition, EGF can enhance the hBMSCs neural differentiation of bFGF, while the Wnt/β-catenin signaling pathway may play a positive regulatory role in these processes.

Abstract TMP45: Nanobiotechnology-based, Ultra-rapid Test For Brain Injuries To Accelerate Differential Diagnosis Of Stroke From Mimics

Introduction: Stroke is the 5th leading cause of death, and a leading cause of long-term disability in the US. Thus, there is a need for a rapid biomarker-based screen that enables an objective and timely diagnosis and better patient outcome; however, the lack of such a technology delays diagnosis and treatment, increases misdiagnosis, and leads to the overuse of thrombolysis in patients with stroke mimics. Methods: Here we present pilot data of a nanobiotechnology based test platform, in which enzyme-functionalized nanoparticles (TET, Tethered Enzyme Technology) are used for ultra-rapid biomarker detection. As proof of concept, we used TET to quantify the enzymatic activity of a widely studied brain injury biomarker, neuron-specific enolase (NSE), in a trial performed at a regional stroke center. Results: Plasma from 36 suspected stroke and 17 asymptomatic subjects (Total N=53) was tested to determine levels of the novel biomarker NSE catalytic activity (NSE-A) versus the conventional NSE protein (NSE-P). Based on clinical diagnoses, our data demonstrate a significant increase in the levels of NSE-A in subjects suffering from injury to neurons (BI, Brain Injury) compared to those with negative diagnoses (Neg, stroke mimics). Moreover, we show that NSE-A provides a considerable diagnostic advantage over the NIH Stroke Scale or NSE-P (Figure 1A-C) in both clinical utility and speed. In diagnosis of stroke mimics (including TIAs and Neg) versus BI, NSE-A showed significantly better performance than NIHSS or NSE-P, as shown by ROC and AUC analyses (Figure 1D). Conclusions: TET-based detection of NSE-A can rapidly differentiate patients suffering a neuronal injury, including stroke, from those presenting with stroke mimics. Upon further development of a point-of-care test for NSE-A and other biomarkers, TET could be an asset to ongoing efforts to streamline stroke patient care, reduce door to needle time, and decrease overall brain injury and long-term disability.

[Effect of transcranial direct current stimulation on neurological injury markers and prognosis in patients with acute and severe carbon monoxide poisoning].

Objective: To observe the effects of transcranial direct current stimulation (tDCS) on nerve injury markers and prognosis in patients with acute severe carbon monoxide poisoning (ASCOP) . Methods: In May 2021, 103 ASCOP patients were treated in the emergency department of Harrison International Peace Hospital of Hebei Medical University from November 2020 to January 2021. The patients were divided into two groups according to whether they received tDCS treatment. The control group (50 cases) were given oxygen therapy (hyperbaric oxygen and oxygen inhalation) , reducing cranial pressure, improving brain circulation and cell metabolism, removing oxygen free radicals and symptomatic support, and the observation group (53 cases) was treated with 2 weeks of tDCS intensive treatment on the basis of conventional treatment. All patients underwent at least 24 h bispectral index (BIS) monitoring, BIS value was recorded at the hour and the 24 h mean value was calculated. Neuron-specific enolase (NSE) and serum S100B calcium-binding protein (S100B) were detected after admission, 3 d, 7 d and discharge. Follow-up for 60 days, the incidence and time of onset of delayed encephalopathy (DEACMP) with acute carbon monoxide poisoning in the two groups were recorded. Results: The NSE and S100B proteins of ASCOP patients were significantly increased at admission, but there was no significant difference between the two groups (P=0.711, 0.326) . The NSE and S100B proteins were further increased at 3 and 7 days after admission. The increase in the observation group was slower than that in the control group, and the difference was statistically significant (P(3 d)=0.045, 0.032, P(7 d)=0.021, 0.000) ; After 14 days, it gradually decreased, but the observation group decreased rapidly compared with the control group, with a statistically significant difference (P=0.009, 0.025) . The 60 day follow-up results showed that the incidence of DEACMP in the observation group was 18.87% (10/53) , compared with 38.00% (19/50) in the control group (P=0.048) ; The time of DEACMP in the observation group[ (16.79±5.28) d] was later than that in the control group[ (22.30±5.42) d], and the difference was statistically significant (P=0.013) . Conclusion: The early administration of tDCS in ASCOP patients can prevent the production of NSE and S100B proteins, which are markers of nerve damage. and can improve the incidence and time of DEACMP.

Reprogramming of Rat Fibroblasts into Induced Neurons by Small-Molecule Compounds In Vitro and In Vivo.

Cell replacement is a promising approach for neurodegenerative disease treatment. Somatic cells such as fibroblasts can be induced to differentiate into neurons by specific transcription factors; however, the potential of viral vectors used for reprogramming to integrate into the genome raises concerns about the potential clinical applications of this approach. Here, we directly reprogrammed rat embryonic skin fibroblasts into induced neurons (iNs) via six small-molecule compounds (SMs) (VPA, CHIR99021, forskolin, Y-27632, Repsox, and P7C3-A20). iNs exhibit typical neuronal morphology, and immunofluorescence showed that more than 96% of the iNs expressed the early neuronal marker class III beta-tubulin (TUJ1) and that more than 91% of iNs expressed the mature neuronal marker neuron-specific enolase (NSE) after 10 days of reprogramming. Quantitative real-time polymerase chain reaction also showed that most iNs expressed the dopaminergic neuron marker tyrosine hydroxylase, the neural marker Nur correlation factor 1, the (γ-aminobutyric acid, GABA) GABAergic neuronal marker GABA, and the cholinergic neuron marker choline acetyltransferase. In addition, we found that cell proliferation decreased during reprogramming and that protein synthesis increased initially and then decreased. SMs were mixed with hydrogels, and the hydrogels were implanted subcutaneously into the backs of rats. After 7 days, the TUJ1 and NSE proteins were expressed in surrounding tissues, indicating that SMs caused reprogramming in vivo. In summary, rat skin fibroblasts can be efficiently reprogrammed into iNs by SMs in vitro and in vivo.

Сравнение динамики биомаркеров нейронспецифической енолазы и протеина S-100 у новорожденных с гипоксически-ишемической энцефалопатией в зависимости от времени начала проведения лечебной гипотермии (0–6 часов и 6–24 часа после родов)

Актуальность. Сегодня остается невыясненным соответствие абсолютных сывороточных концентраций нейронспецифической енолазы (NSE) и протеина S-100 степени тяжести и возможным последствиям гипоксически-ишемической энцефалопатии (ГИЭ), а также динамика этих показателей на протяжении острого периода ГИЭ в зависимости от времени начала проведения лечебной гипотермии. Цель: исследовать динамику сывороточных показателей нейронспецифической енолазы и протеина S-100 у доношенных новорожденных в течение острого периода ГИЭ в зависимости от времени начала проведения лечебной гипотермии. Материалы и методы. Проспективное одноцентровое когортное исследование 205 доношенных младенцев, которые в 2012–2017 гг. находились на лечении в отделении анестезиологии и интенсивной терапии для новорожденных с диагнозом «гипоксически-ишемическая энцефалопатия». Дети были стратифицированы по времени от рождения до поступления в отделение интенсивной терапии (ОАИТН). Были исследованы сывороточные концентрации нейронспецифической енолазы и протеина S-100 в 1, 3 и 5-й день лечения как в целом во всей когорте, так и в группах: 0–6 часов (группа 1, n = 56) и более 6 часов после рождения (группа 2, n = 149). Результаты. Динамика S-100 была существенной в течение 5 дней в обеих группах новорожденных (p &lt; 0,001). Однако не было найдено достоверного различия в тенденции изменения концентрации протеина S-100 в течение первых 5 дней в обеих группах (р = 0,082). Также не было статистически значимой разницы между пациентами, поступившими в первые 6 часов и позже, относительно значения S-100 (р = 0,320) в течение всех пяти дней, за исключением первого дня при поступлении (р = 0,002). Не было найдено статистически значимой разницы уровня NSE в группах как в динамике от 1-го до 5-го дней (р = 0,217), так и относительно раннего (0–6 часов) или позднего (более 6 часов) поступления в ОАИТН (р = 0,845). Нет также достоверного различия концентрации NSE между группами (р = 0,719). Выводы. Отсутствие достоверного различия динамики уровня протеина S-100 и NSE у новорожденных до 6 часов и после от момента рождения свидетельствует о возможности начала проведения лечебной гипотермии более чем через 6 часов после родов, если по организационным причинам ее не успели начать раньше.

Serum NSE and S100B protein levels for evaluating the impaired consciousness in patients with acute carbon monoxide poisoning.

The aim of this study was to investigate the associations between the levels of neuron-specific enolase (NSE) and S100B protein and coma duration, and evaluate the optimal cut-off values for prediction coma duration ≥ 72 hours in patients with acute carbon monoxide poisoning (ACOP).A total of 60 patients with ACOP were divided into 3 following groups according to their status of consciousness and coma duration at admission: Awake group [Glasgow Coma Scale score (GCS score) ≥ 13 points], Coma < 72 hours group (GCS score < 13 points and coma duration < 72 h), and Coma ≥ 72 hours group (GCS score < 13 points and coma duration ≥ 72 h). The levels of serum NSE and S100B protein were measured after admission.There were significant differences in GCS score, carbon monoxide (CO) exposure time, NSE, and S100B levels between the Coma ≥ 72 h group and the Awake group, and between the Coma < 72 h group and the Awake group. Significant differences in GCS score, NSE, and S100B levels were also found between Coma ≥ 72 h group and Coma < 72 h group. Correlation analysis showed that NSE and S100B were positively correlated (rs = 0.590, P < .01); NSE and S100B were negatively correlated with GCS score (rs = -0.583, rs = -0.590, respectively, both P < .01). The areas under the curve (AUCs) of NSE, S100B, and GCS score to predict the coma duration ≥ 72 hours were 0.754, 0.791, and 0.785, respectively. Pairwise comparisons did not show differences among the 3 groups (all P > .05). The sensitivity and specificity of NSE prediction with a cut-off value of 13 μg/L were 80% and 64%, respectively, and those of S100B prediction with a cut-off value of 0.43 μg/L were 70% and 88%, respectively.The NSE and S100B protein levels were significantly correlated with the degree of impaired consciousness and had the same clinical value in predicting coma duration of ≥ 72 hours in patients with ACOP.

The Possible Role of Neuron Specific Enolase and Neurofilament Light Protein as Markers for Organophosphorus-induced Neurotoxicity

Background: Acute organophosphorus (OP) poisoning is a common toxic emergency all over the worldespecially in the developing countries as Egypt. Neurological damage occurs after exposure to thesecompounds can lead to respiratory failure and death. Thus, it is important to identify the severity of poisoningand predict the need to ventilation support or death.Methods: A prospective study that included 50 adult patients presented with neurological manifestationsafter acute OP poisoning admitted to the ICU of Poison Control Center of Ain shams university (PCC-ASU),and 25 healthy volunteers. Meusering levels of Neuron Specific Enolase (NSE) and Neurofilament Light(NFL) protein and correlate this with severity according to APACHE II score and outcome of patients.Conclusion: There was a significant difference between cases and controls among levels of NSE and NFLprotein, also there was a significant correlation between NSE and NFL protein levels and prediction of bothM.V. need and mortality, so NSE and NFL protein can be used as markers for neurological damage afterexposure to OP compounds.

Serum Neuron-Specific Enolase Levels Associated with Connectivity Alterations in Anterior Default Mode Network after Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is the most prevalent neurological insult and leads to long-lasting cognitive impairment. Neuroimaging studies have discovered abnormalities in brain network connectivity following mTBI as the underlying neural basis of cognitive deficits. However, the pathophysiologic mechanisms involved in imaging alterations remain elusive. Proteins neuron-specific enolase (NSE) and ubiquitin C terminal hydrolase 1 are reliable markers for neuronal cell-body damage, both of which have been demonstrated to be increased in serum following mTBI. Therefore, we conducted a longitudinal study to examine relationships between abnormal brain network connectivity and serum neuronal biomarkers and their associations with cognitive recovery following mTBI. Sixty patients were followed-up at 1 week and 3 months post-injury and 41 controls were recruited. Resting-state functional magnetic resonance imaging was used to build a functional connectivity matrix within large-scale intrinsic networks, and their topological properties were analyzed using graph theory measures. We found that, compared with controls, mTBI patients showed significant decreases in a number of nodal characteristics in default mode network (DMN), salience network, and executive network (p < 0.05, false discovery rate corrected) at 3 months post-injury. Linear regression analysis found elevated serum NSE in acute phase could predict lower efficiency and degree centrality of anterior DMN at 3 months post-injury. In addition, efficiency and degree centrality of anterior DMN were negatively associated with working memory. Our study showed neuronal injury was associated with alterations in brain network connectivity after mTBI. These findings can facilitate capability to predict the brain functional outcomes and cognitive recovery in mTBI.

Role of Diffusion Tensor Imaging Combined with Neuron-Specific Enolase and S100 calcium-binding protein B Detection in Predicting the Prognosis of Moderate and Severe Traumatic Brain Injury

Background Traumatic brain injury (TBI) seriously affects the quality of life of patients. The present study evaluated the role of diffusion tensor imaging (DTI) combined with Neuron-Specific Enolase (NSE) and S100 calcium-binding protein B (S100B) protein in predicting the prognosis of moderate and severe TBI. Methods The TBI patients were divided into moderate TBI (TBIm) and severe TBI (TBIs) groups according to the Glasgow Coma Scale (GCS) after admission. The patients were then divided into good and poor prognosis groups according to the Glasgow Outcome Scale (GOS); moreover, their follow-ups were recorded at 3 and 6 months after injury. This study also included 65 healthy individuals with matched age and gender as the control group. The fractional anisotropy (FA) values of DTI, serum neuron-specific enolase (NSE), and S100B protein levels were detected in this study. The data were analyzed in SPSS software (version 22.0) to evaluate the role of DTI combined with NSE and S100B protein in predicting the prognosis in TBIm and TBIs. Results: After TBI, the FA values of DTI in the TBI group were lower than those in the control group (P&lt;0.05); moreover, the serum NSE and S100B values in the TBI group were higher than those in the control group (P&lt;0.05). In the TBIm patients, the FA values of the corpus callosum in the good prognosis group were higher than that in the poor prognosis group (P&lt;0.05); however, there was no significant difference between the two groups regarding the FA values of the internal capsule and the cerebral peduncle (P&gt;0.05). The serum levels of NSE and S100B in the good prognosis group were significantly lower than those in the poor prognosis group (P&lt;0.05). In the TBIs patients, the FA value of all areas in the good prognosis group was significantly higher than that in the poor prognosis group (P&lt;0.05). However, there was no significant difference between the two prognosis groups regarding the serum levels of NSE and S100B (P&gt;0.05). Conclusion Although DTI combined with NSE and S100B protein can effectively predict the prognosis of patients with moderate and severe TBI in the early stages, various other measures have been used in the studies to predict the prognosis of TBI patients. Accordingly, comparison with other measures is essential in further studies.

Icariside II promotes the differentiation of human amniotic mesenchymal stem cells into dopaminergic neuron-like cells.

The purpose of thisstudy is to observe the effect of icariside II (ICS II) on the differentiation of human amniotic mesenchymal stem cells (hAMSCs) into dopaminergic neuron-like cells, the involvement of PI3K signaling pathway inhibitors. After identifying hAMSCs by flow cytometry, hAMSCs were induced and treated with ICS II at 10 μmol/L, 3 μmol/L, 1 μmol/L, and 0 μmol/L. hAMSCs in the LY294002+3μM ICS II group were pretreated with 20 μmol/L LY294002, a PI3K-specific inhibitor, for 1 h, and then hAMSCs were induced with 3 μmol/L ICS II. On the 21st day of induction, immunofluorescence was used to detect expression of the neuronal nuclei (NeuN), neuron-specific enolase (NSE), microtubule-associated protein-2 (MAP-2), glial fibrillary acidic protein (GFAP), and tyrosine hydroxylase (TH) antigens in each induced cell group. Western blotting was used to detect the relative protein expression of NSE, MAP-2, GFAP, and TH. ELISA was used to detect the dopamine concentration in the induction medium supernatant of each group. After 21 d of ICS II induction, immunofluorescence showed that GFAP expression was not obvious in any hAMSC group. The NeuN, NSE, MAP-2, and TH fluorescent proteins were expressed in each group. NeuN was expressed in the nucleus and cytoplasm, while NSE, MAP-2, and TH were mainly expressed in the cytoplasm. The positive cell rates of NeuN, NSE, MAP-2, and TH in the 10 μmol/L, 3 μmol/L, and 1 μmol/L ICS II groups were higher than those in the LY294002+3μM ICS II and control groups. After 21 d of induction, the Western blot results showed that the protein expression levels of NSE, MAP-2, and TH in the 10 μmol/L, 3 μmol/L, and 1 μmol/L ICS II groups were significantly higher than those in the LY294002+3μM ICS II and control groups. The MAP-2 protein expression levels in the 10 μmol/L and 3 μmol/L groups were higher than that in the 1 μmol/L group. After 21 d of induction, the dopamine concentrations in the culture supernatants of the 10 μmol/L, 3 μmol/L, and 1 μmol/L ICS II groups were higher than those in the LY294002+3μM ICS II and control groups. In our experiment, ICS II induced hAMSCs to differentiate into dopaminergic neuron-like cells, and the optimal concentration range of ICS II was 3-10 μmol/L. Moreover, the PI3K signaling pathway is involved in the above differentiation process.

Effects of Astragalus Polysaccharides Nanoparticles on Cerebral Thrombosis in SD Rats.

ObjectiveTo investigate the efficacy and improvement of Astragalus polysaccharides (APS) and APS-nano on cerebral thrombosis in rats.MethodsA total of 72 SD rats were randomly divided into NC group, Model group, APS-Nano group, and APS group. The cerebral thrombosis Model of SD rats was established by injecting compound thrombus inducer into the internal carotid artery. After 14 days of different intervention treatments, the TTC staining of brain tissue were performed, and A/left brain wet weight ratio, left brain/right brain wet weight ratio, blood rheology indexes, and coagulation function indexes of cerebral thrombosis were measured. ELISA was used to measure the contents of thromboxane 2 (TXB2), 6-keto-prostaglandin F1α (6-Keto-PGF1α), tissue factor (TF), neuron-specific enolase (NSE), S-100β, catenin (CAT), superoxide dismutase (SOD), as well as malondialdehyde (MDA). The binding specificity between miR-885-3p and TF was verified by the double-luciferin reporting experiment, and western blot was used to measure the expression level of TF protein.ResultsCompared with the Model group, after treatment with APS-nano or APS, the ratio of left brain/right brain wet weight decreased significantly. Whole blood low shear viscosity (WBLSV), whole blood high shear viscosity (WBHSV), plasma viscosity (PV), and erythrocyte aggregation index (Arbc) was all reduced. In addition, prothrombin time (PT) and activated partial thromboplastin time (APTT) were increased, and fibrinogen (FIB) content was decreased. The expression of TXB2, 6-Keto-PGF1α, and TF showed a downward trend. Similarly, the expression of TF protein was decreased. Furthermore, the contents of NSE and S-100β proteins were all decreased, whereas the contents of CAT and SOD were increased, and the contents of MDA was decreased. At the same dose, compared with APS treatment, APS-nano treatment had a significant inhibitory effect on cerebral thrombosis in rats. Finally, we found that TF is a target gene of miR-885-3p and specifically binds to miR-885-3p.ConclusionAPS has a significant inhibitory effect on the formation of cerebral thrombosis induced by compound thrombus inducers. Moreover, APS-nano has a more significant inhibitory effect on cerebral thrombosis. Meanwhile, the regulation of miR-885-3p regulating TF expression may be related to the occurrence of cerebral thrombosis.

Dexmedetomidine is superior to midazolam for sedation and cerebral protection in postoperative hypertensive intracerebral hemorrhage patients: a retrospective study.

ObjectiveDexmedetomidine has a good sedative effect and does not affect the judgment of the patient's consciousness level. However, its effectiveness for sedation and cerebral protection after craniotomy in hypertensive intracerebral hemorrhage (HICH) patients is unknown.MethodsA retrospective study of 164 postoperative HICH patients who underwent sedation with dexmedetomidine or midazolam was conducted. The Ramsay sedation score, mean arterial pressure (MAP), heart rate (HR), pulse oxygen saturation (SpO2), and respiratory rate were measured at the indicated time points. Human soluble protein-100β (S-100β) and neuron-specific enolase (NSE) levels were also compared between the two groups.ResultsDexmedetomidine treatment showed a significantly better effect than midazolam on decreasing the frequency of apparent agitation. The MAP and HR, but not the SpO2, were significantly decreased and lower than those in midazolam group. Detection of plasma S-100β and NSE proteins revealed a significant decrease in the dexmedetomidine group compared with the midazolam group. The 6-month follow-up evaluation indicated a significantly better prognosis of postoperative HICH patients treated with dexmedetomidine than for those treated with midazolam.ConclusionsDexmedetomidine is effective for sedation in postoperative HICH patients and may be beneficial for their outcome.

Sodium valproate combined with levetiracetam in pediatric epilepsy and its influence on NSE, IL-6, hs-CRP and electroencephalogram improvement.

Efficacy of sodium valproate combined with levetiracetam (LEV) in pediatric epilepsy and its influence on neuron-specific enolase (NSE), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) as well as electroencephalogram (EEG) improvement were studied. Patients (n=100) with pediatric epilepsy admitted to and treated in Xiantao First People's Hospital Affiliated to Yangtze University from December 2015 to 2018 were enrolled in this study and randomly divided into observation group (n=50) and control group (n=50). Sodium valproate was administered in the control group, and the treatment with LEV was combined with sodium valproate in the observation group. After 12 weeks the cognitive function of patients was assessed using the Mini-Mental State Examination (MMSE) scale, Montreal cognitive assessment (MoCA) scale and Wechsler Memory Scale-Revised in China (WMS-RC). The quality of life (QOL) of patients was evaluated with the QOL in epilepsy-31 inventory (QOLIE-31) scale and Barthel Index, and blood was drawn from the patients to detect the neurological function indicators [NSE and glial fibrillary acidic protein (GFAP)] and inflammatory indicators (IL-6, IL-2 and hs-CRP). After treatment, the incidence rates of adverse reactions notably declined in the observation group (P<0.05), and the improvement in the cognitive function in the observation group were both superior to those in the control group (P<0.05). Observation group had lowered content of NSE, GFAP, IL-6, hs-CRP and IL-2 (P<0.05), and α wave was markedly decreased, but θ and δ waves were notably increased in the observation group (P<0.05). In the treatment of pediatric epilepsy, sodium valproate combined with LEV produces better efficacy, fewer adverse reactions, significantly improves patients' QOL and notably lowers the content of NSE, IL-6 and hs-CRP with notable EEG improvement, so it is a safe and reliable treatment that is worth popularization.

Effect of dexmedetomidine on brain function and hemodynamics in patients undergoing lung cancer resection

Effect of dexmedetomidine on the brain function and hemodynamics in patients undergoing lung cancer resection were explored. Eighty-seven patients with lung cancer undergoing lung cancer resection in Weifang People's Hospital from January 2014 to June 2018 were enrolled in this study. Patients conventionally anesthetized by propofol, midazolam, sufentanil, or cisatracurium besilate (41 cases) were assigned to the control group and those anesthetized by conventional anesthetic and dexmedetomidine (46 cases) were assigned to the research group. The hemodynamic parameters, neuron-specific enolase (NSE), and astrocyte S-100p protein (S-100β) were compared between the two groups before induction (T0), 5 min after induction (T1), at the end of surgery (T2), time of extubation (T3), and 5 min after extubation (T4). The cognitive function of patients was graded by the mini-mental state examination (MMSE) after patients recovered from anesthesia. In both the control group and the research group, the levels of mean arterial pressure (MAP), heart rate (HR), and central venous pressure (CVP). were statistically higher at T2 and T3 than those at T0 (all P<0.05). The levels of MAP, HR, and CVP were statistically lower in the research group than those in the control group at T2 and T3 (P<0.05). The levels of serum NSE and S100β protein in the research group and the control group increased at T2, T3, and T4, the control group was higher than the research group at each time point, and the difference was statistically significant (P<0.05). Comparison of the MMSE score and the total case number of adverse reactions between the two groups showed no statistical difference (both P>0.05). The MMSE score was positively correlated with the serum levels of NSE and S100β in the two groups (r-values were 0.661 and 0.585, P<0.05). Dexmedetomidine can effectively protect patients' perioperative brain function with small impacts on perioperative hemodynamics, so it is worthy of clinical application.

Peptides of neuron specific enolase as potential ASD biomarkers: From discovery to epitope mapping

Autism spectrum disorder (ASD) is an important health issue and affects 1 in 59 children in the US. Prior studies determined that maternal autoantibody related (MAR) autism is thought to be associated with ~23% of ASD cases. We previously identified seven MAR-specific autoantigens including CRMP1, CRMP2, GDA, LDHA, LDHB, STIP1, and YBX1. We subsequently described the epitope peptide sequences recognized by maternal autoantibodies for each of the seven ASD-specific autoantigens. The aim of the current study was to expand upon our previous work and identify additional antigens recognized by the ASD-specific maternal autoantibodies, as well as to map the unique ASD-specific epitopes using microarray technology. Fetal Rhesus macaque brain tissues were separated by molecular weight and a fraction containing bands between 37 and 45 kDa was analyzed using 2-D gel electrophoresis, followed by peptide mass mapping using MALDI-TOF MS and TOF/TOF tandem MS/MS. Using this methodology, Neuron specific enolase (NSE) was identified as a target autoantigen and selected for epitope mapping. The full NSE sequence was translated into 15-mer peptides with an overlap of 14 amino acids onto microarray slides and probed with maternal plasma from mothers with an ASD child and from mothers with a Typically Developing child (TD) (ASD = 27 and TD = 21). The resulting data were analyzed by T-test. We found 16 ASD-specific NSE-peptide sequences for which four sequences were statistically significant (p < 0.05) using both the t-test and SAM t-test: DVAASEFYRDGKYDL (p = 0.047; SAM score 1.49), IEDPFDQDDWAAWSK (p = 0.049; SAM score 1.49), ERLAKYNQLMRIEEE (p = 0.045; SAM score 1.57), and RLAKYNQLMRIEEEL (p = 0.017; SAM score 1.82). We further identified 5 sequences that were recognized by both ASD and TD antibodies suggesting a large immunodominant epitope (DYPVVSIEDPFDQDDWAAW). While maternal autoantibodies against the NSE protein are present both in mothers with ASD and mothers of TD children, there are several ASD-specific epitopes that can potentially be used as MAR ASD biomarkers. Further, studies including analysis of NSE as a target protein in combination with the previously identified MAR ASD autoantigens are currently underway.

Value of NSE and S100 Protein of Kawasaki Disease with Aseptic Meningitis in Infant.

The cerebrospinal fluid content was examined for concentrations of S100 protein and neuron-specific enolase (NSE) in two diseases, Kawasaki disease (KD) with aseptic meningitis (1-3 months) and purulent meningitis (PM), to determine whether or not these measuremets could be used in early diagnosis. The content of cerebrospinal fluid S100 protein of KD with aseptic meningitis and PM were significantly higher than those in the control group. There was also a difference between KD and purulent meningitis (PM). The concentration of NSE was highest in the encephalitis group, which was statistically different from control group. However, there was no difference between the KD and control groups. The levels of S100 protein and NSE of KD with aseptic meningitis were lower than those in PM, indicating that the extent of neuronal damage is significantly lower than of the enchephalitis group. The area under the curve (AUCs) of the receiver operating characteristic (ROC) curve for S100 and NSE were both 0.972. The S100 threshold was 0.4315, the sensitivity was 92.1%, and the specificity was 100%, while the NSE threshold was 9.325, sensitivity 92.1%, and specificity 90%. The combined detection of NSE and S100 levels in the cerebrospinal fluid can be used for the differential diagnosis of KD with aseptic meningitis and purulent meningitis.

&lt;p&gt;NSE from diffuse large B-cell lymphoma cells regulates macrophage polarization&lt;/p&gt;

Background/aims: Diffuse large B-cell lymphoma (DLBCL) is a highly common type of malignant and heterogeneous non-Hodgkin’s lymphoma. Tumor-associated macrophages, specially the M2-type, promote tumor progression and drug resistance. The clinical outcome of patients with high neuron-specific enolase (NSE) expression is worse than that with low NSE expression. The tumor-promoting mechanism of NSE, however, remains unclear. This study explored the role of NSE in macrophage polarization associated with the immune microenvironment of DLBCL.Results: Our results showed that NSE protein expression was higher in lymphoma cell lines than in the B lymphocytes. Functional studies demonstrated that upregulation of NSE in lymphoma cells could promote M2 polarization and migration ability of macrophage, thereby consequently promoting the progression of lymphoma in vitro and in vivo. Further mechanism studies revealed that lymphoma-derived exosomes could mediate NSE into macrophages, NSE enhanced nuclear p50 translocation with subsequent defective classical nuclear factor-κB activity in macrophages.Conclusions: These results indicate that NSE may be a potential target for lymphoma therapy and a prognosis marker for lymphoma.

Nauclea latifolia stem-bark extract protects the prefrontal cortex from valproic acid - induced oxidative stress in rats: Effect on B-cell lymphoma and neuron specific enolase protein expression

Nauclea latifolia stem-bark (NLS) is widely utilized for broad spectrum pathologies. The study evaluated the protective effects of NLS extract supplemented along with valproic acid on oxidative stress markers, and neuron specific enolase (NSE) and B cell lymphoma 2 (bcl-2) protein expressions in prefrontal cortex of rats. The NLS extract was administered in three doses (50, 100, 200mg/kg) after pre-treatment of the experimental animals with high dose valproic acid (VPA) (500 mg/kg) orally daily by subacute exposure for 28 days. The rats were sacrificed and the prefrontal cortex (PFC) of the brain abstracted and homogenized in ice for biochemical assays to estimate the levels oxidative stress markers; histopathological examination to reveal the histomorphorgical changes and immunohistochemistry to examine effect on NSE andbcl-2protein expressions. The findings revealed significant (P < 0.05 – 0.001) elevation of oxidative stress induced by VPA. The NLS extract supplementation mediate significant elevation of the levels of reduced glutathione (P< 0.05 – 0.01), antioxidant enzymes [glutathione peroxidase (P< 0.001), superoxide dismutase (P < 0.001), catalase (P< 0.05 – 0.01) and glutathione-s-transferase (P < 0.05 – 0.01)] and significant decline of lipid peroxidation marker, malondialdehyde, (NLS group vs diseases control group (P < 0.001). The NLS extract studied down-regulated NSE at the prefrontal cortex preventing neuronal damage but no effect on bcl-2 protein expression. We conclude that NLS extract has potential to mitigate VPA induced neurotoxicity by obliterating oxidative stress and down regulating NSE expression, effects demonstrating probable therapeutic role in neurodegenerative diseases.