현훈 환자 Neuron Specific Enolase의 임상적 의의

김원주,김선곤,유철형,김원찬,김용덕,최영철,이명식 대한신경과학회 1998 대한신경과학회지 Vol.16 No.4

Combined Method of Neuronal Cell-Inducible Vector and Valproic Acid for Enhanced Gene Expression under Hypoxic Conditions

윤여민,백다예,Dongsu Lee,Eunji Cheong,김장환,오진수,Yoonha Oh 한국조직공학과 재생의학회 2020 조직공학과 재생의학 Vol.17 No.1

BACKGROUND: Gene therapy shows the ability to restore neuronal dysfunction via therapeutic gene expression. The efficiency of gene expression and delivery to hypoxic injury sites is important for successful gene therapy. Therefore, we established a gene/stem cell therapy system using neuron-specific enolase promoter and induced neural stem cells in combination with valproic acid to increase therapeutic gene expression in hypoxic spinal cord injury. METHODS: To examine the effect of combined method on enhancing gene expression, we compared neuronal cellinducible luciferase levels under normoxia or hypoxia conditions in induced neural stem cells with valproic acid. Therapeutic gene, vascular endothelial growth factor, expression with combined method was investigated in hypoxic spinal cord injury model. We verified gene expression levels and the effect of different methods of valproic acid administration in vivo. RESULTS: The results showed that neuron-specific enolase promoter enhanced gene expression levels in induced neural stem cells compared to Simian Virus 40 promoter under hypoxic conditions. Valproic acid treatment showed higher gene expression of neuron-specific enolase promoter than without treatment. In addition, gene expression levels and cell viability were different depending on the various concentration of valproic acid. The gene expression levels were increased significantly when valproic acid was directly injected with induced neural stem cells in vivo. CONCLUSION: In this study, we demonstrated that the combination of neuron-specific enolase promoter and valproic acid induced gene overexpression in induced neural stem cells under hypoxic conditions and also in spinal cord injury depending on valproic acid administration in vivo. Combination of valproic acid and neuron-specific enolase promoter in induced neural stem cells could be an effective gene therapy system for hypoxic spinal cord injury.

급성 뇌경색에서 시간 경과에 따른 혈청 신경원 특이 에놀라제(neuron specific enolase)의 변화

구본대,정경천 대한신경과학회 2009 대한신경과학회지 Vol.27 No.1

Background: Neuron-specific enolase (NSE) is a useful indicator of neuronal injury in acute cerebral infarction. We investigated the changes in serial serum NSE levels in patients with acute cerebral infarction. Methods: We measured serial serum NSE levels at 24, 48, 72, and 96 hours, and 2 weeks after the onset of cerebral infarction in 30 patients (15 territorial and 15 lacunar infarctions). We also measured the NSE levels in age-matched controls (n=15) who had no evidence of acute stroke or other neurological disorders. The NSE level was measured using a radioimmunoassay. Results: The initial serum NSE level was significantly higher in the cerebral infarction group than in the control group (6.6±2 vs 4.7±1.6 ng/mL [mean±SD], p=0.006). This difference was also observed between the territorial and lacunar infarction groups until 72 hours after the cerebral infarction. The serum NSE level peaked at 72 hours after the infarction in both lacunar and territorial infarction groups. The correlation between the NSE level and the score on the NIH Stroke Scale was strongest at 48 hours after the cerebral infarction (r=0.469). Conclusions: Serum NSE level can be a good indicator for distinguishing lacunar from territorial infarction during the acute stage of cerebral infarction. Background: Neuron-specific enolase (NSE) is a useful indicator of neuronal injury in acute cerebral infarction. We investigated the changes in serial serum NSE levels in patients with acute cerebral infarction. Methods: We measured serial serum NSE levels at 24, 48, 72, and 96 hours, and 2 weeks after the onset of cerebral infarction in 30 patients (15 territorial and 15 lacunar infarctions). We also measured the NSE levels in age-matched controls (n=15) who had no evidence of acute stroke or other neurological disorders. The NSE level was measured using a radioimmunoassay. Results: The initial serum NSE level was significantly higher in the cerebral infarction group than in the control group (6.6±2 vs 4.7±1.6 ng/mL [mean±SD], p=0.006). This difference was also observed between the territorial and lacunar infarction groups until 72 hours after the cerebral infarction. The serum NSE level peaked at 72 hours after the infarction in both lacunar and territorial infarction groups. The correlation between the NSE level and the score on the NIH Stroke Scale was strongest at 48 hours after the cerebral infarction (r=0.469). Conclusions: Serum NSE level can be a good indicator for distinguishing lacunar from territorial infarction during the acute stage of cerebral infarction.

혈청 neuron specific enolase를 이용한 심정지후 신경학적 예후의 예측

강용선,정성필,박기일,김승환,김태승,이한식 大韓應急醫學會 1999 대한응급의학회지 Vol.10 No.2

Background: The purpose of this study was to determine that the assessment of serum neuron specific enolase(NSE) could provide a reliable early predictor of neurologic outcome after cardiac arrest. Methods: Prospective, observational study was performed from April 1996 to March 1998 at a university teaching hospital ED. Serum NSE concentrations were analysed twice at 24 and 48 hours after return of spontaneous circulation(ROSC). Neurologic outcome was categorized using cerebral performance category(CPC). Results: Twenty-nine patients(16 were men) were enrolled during the study period. The mean age was 50.8 years. Nine(31%) of them showed good outcome defined as CPC 1-3, and 20(69%) patients showed bad outcome defined as CPC 4-5. In the good outcome group, the serum NSE was revealed 33.8±9.3 ng/ml at 24 hours, 34.0±4.73 ng/ml at 48 hours. While in the bad outcome group, it was 99.5±11.7 ng/ml and 114.6±15.8 ng/ml. The NSE at 48hr after ROSC was more prescise than that of 24hr. When the cutoff value of 50 ng/ml at 48hr, the sensitivity was 82%, and specificity was 93%. Conclusion: This study suggest that the serum NSE may represent a valuable, noninvasive, and useful clinical tool for prediction of neurologic outcome after cardiac arrest.

한번의 간질발작 후 혈청 Neuron-Specific Enolase 농도 변화

최승호,박영춘,이장준,임정근,김지언,이상도 啓明大學校 醫科大學 1999 계명의대학술지 Vol.18 No.4

An increase in neuron-specific enolase (NSE) levels in serum and CSF has been shown to be an useful marker of brain damage after stroke, global ischemia, and coma. We report the changes of serum NSE levels after seizure attacks in epileptic patients compared with the levels in normal controls and epileptic patients without seizure attack at least 7 days (epileptic controls). Twenty-four seizures were included in this study. Blood was drawn within 1 hour, at 12 hour, 24 hour, and 48 hour after seizure attack. Serum NSE levels were measured with radioimmunoassay. The mean NSE levels for normal controls and epileptic controls were 6.94 ng/ml and 7.46 ng/ml, respectively. There were significant increase in level of serum NSE measured within 1 hour after seizure attack in epileptics compared with the level in normal controls (15.10ng/ml versus 6.94ng/ml, p<0.05) and epileptic controls (15.10ng/ml versus 7.46ng/ml, p<0.05). Serum NSE measured at 12 hours after seizure also increased compared with normal controls (12.32ng/ml versus 6.94ng/ml, p<0.05) and epileptic controls (12.43ng/ml versus 7.46ng/ml, p<0.05). Between normal controls and epileptic controls, there were no significant difference in serum NSE levels. We conclude that serum NSE level was elevated in epileptic patients who had seizure attack within 12 hours. Serum NSE levels can be useful marker for seizure within 12 hours after onser. The elevated serum NSE level after single seizure attack may suggest that the brain was injured in single seizure.

Elecsys Neuron-Specific Enolase의 수행능 평가

김수경,정태동,이우창,전사일,민원기 대한진단검사의학회 2015 Laboratory Medicine Online Vol.5 No.2

Background: Neuron-specific enolase (NSE) is an enzyme specifically found in neurons and neuroendocrine tissue. It is a common marker for small cell lung cancer diagnosis and is also useful as a predictor of brain damage. This study evaluates the performance of Elecsys NSE (Roche Diagnostics, Switzerland), an electrochemiluminescent immunoassay. Methods: The precision, linearity, limit of detection, and reference interval of the Elecsys NSE, as well as the correlation between Elecsys NSE and ELSA-NSE (Cis-Bio International, France) were evaluated in accordance with the Clinical Laboratory Standards Institute (CLSI) guidelines. PreciControl Tumor Marker (Roche Diagnostics), patient sera, and sera from healthy individuals were used for the analysis. Results: The measured coefficient of variation for the assay was below 3%, and it demonstrated linearity from 0.20 to 234.5 ng/mL. The detection limit was 0.032 ng/mL and the reference interval ranged from 0.05 to 16.3 ng/mL. Compared with the ELSA-NSE assay, the correlation coefficient was 0.9128. Conclusions: The Elecsys assay showed suitable precision, linearity, limit of detection and reference range for clinical laboratory use; however, the correlation coefficient of Elecsys NSE as compared to ELSA-NSE was below 0.975. This result may be associated with the use of different monoclonal antibodies in the two different NSE assays. Elecsys NSE demonstrated a high sensitivity without the use of radioactive reagents; therefore, Elecsys NSE will be quite useful for NSE analysis in the clinical laboratory setting. 배경: 신경원특이에놀라제(neuron specific enolase, NSE)는 신경세포와 말초 신경내분비세포에 존재하며, 특히 소세포폐암의 표지자 및 뇌손상의 예측인자로 유용한 것으로 알려져 있다. Elecsys NSE (Roche Diagnostics, Switzerland)는 NSE를 전기화학적발광면역법으로 측정하는 검사법으로, 본 연구는 이의 수행능을 평가하고자 하였다. 방법: CLSI 지침에 따라 Elecsys NSE 검사법의 정밀도, 직선성, 검출한계, 참고구간, 기존 장비와의 상관성을 평가하였다. 정밀도 평가를 위해 Elecsys NSE의 전용 대조물질인 PreciControl Tumor Marker 1과 2 (Roche Diagnostics)를 사용하였고, 직선성 평가를 위해 고농도 환자 검체와 PreciControl Tumor Marker 1을 사용하였다. 검출한계는 완충액 및 희석한 환자검체를 사용하였다. 참고 구간검증은 정상인 검체를 사용하였다. 기존장비와의 상관성평가는 환자 검체를 사용하여 RIA 방법인 ELSA-NSE (Cis-Bio International, France)와 비교하였다. 결과: NSE의 총 정밀도는 저농도와 고농도에서 모두 3% 이내였고, 0.20-234.5 ng/mL 범위에서 직선성을 나타내었다. 검출한계는 0.032 ng/mL였다. 참고구간은 0.05-16.3 ng/mL로 제조사가 제시한 구간을 만족하였다. RIA와의 상관성 평가에서 상관계수는 0.9128이었다. 결론: Elecsys NSE는 NSE 측정에 있어 정밀도, 직선성이 우수하였고, 제조사의 검출한계와 참고구간을 만족하였다. 다만, 기존 RIA 장비와의 상관성이 낮았는데, 이는 검사키트마다 서로 다른 단일클론항체를 사용한 것이 원인일 수 있다. Elecsys NSE는 방사성동위원소로 인한 위험이 없으며, 민감도가 높아 일선 검사실에서의 NSE 분석장비로써 적합할 것으로 판단되었다.

위 선암종내 Neuron Specific Enolase 양성 세포의 발현 양상

최기영,김용일 대한병리학회 1991 Journal of Pathology and Translational Medicine Vol.25 No.4

High Serum Levels of Serum 100 Beta Protein, Neuron-specific Enolase, Tau, Active Caspase-3, M30 and M65 in Children with Autism Spectrum Disorders

Hamza Ayaydın,Adnan Kirmit,Hakim Çelik,İsmail Akaltun,İsmail Koyuncu,Şermin Bilgen Ulgar 대한정신약물학회 2020 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.18 No.2

Objective: The purpose of this study was therefore to investigate whether neuronal, axonal, and glial cell markers (Neuron-specific enolase [NSE], tau, serum 100 beta protein [S100B], respectively) and apoptosis markers (active caspase 3, M30, M65) and whether these parameters can be used as diagnostic biomarkers in autism spectrum disorders (ASD). Methods: This study measured the serum S100B, NSE, tau, active caspase 3, M30, and M65 levels in 43 patients with ASD (aged 3−12 years) and in 41 age- and sex-matched healthy controls. ASD severity was rated using the Childhood Autism Rating Scale. The serum levels were determined in the biochemistry laboratory using the ELISA technique. The receiver operator characteristics curve method was employed to evaluate the accuracy of the parameters in diagnosing ASD. Results: Serum S100B, tau, NSE, active caspase-3, M30, and M65 levels were significantly higher in the patient group than in the control group (p < 0.001, p = 0.002, p = 0.002, p = 0.005, p < 0.001, and p = 0.004, respectively). The cut-off value of S100B was 48.085 pg/ml (sensitivity: 74.4%, specificity: 80.5%, areas under the curve: 0.879, p < 0.001). Conclusion: Apoptosis increased in children with ASD, and neuronal, axonal, and glial cell injury was observed. In addition, S100B may be an important diagnostic biomarker in patients with ASD. Apoptosis, and neuronal, axonal and astrocyte pathologies may play a significant role in the pathogenesis of ASD, and further studies are now required to confirm this.

Comparison of the prognostic performance between neuron-specific enolase and S100 calcium-binding protein B obtained from cerebrospinal fluid; A sequential analysis in out-of-hospital cardiac arrest survivors who underwent target temperature management

강창신,박정수 대한응급의학회 2020 대한응급의학회 학술대회초록집 Vol.2020 No.2

Introduction Measuring the value of cerebrospinal fluid (CSF) prognostic biomarkers has been suggested to enhance accuracy and early prognostication in out-of-hospital cardiac arrest (OHCA) survivors. This study aimed to compare the prognostic performance of neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) obtained from CSF in OHCA survivors. Material & Method This was a prospective single-center study conducted from February 2019 to August 2020. The CSF samples of NSE and S100B were obtained immediately after return of spontaneous circulation (ROSC) and at 24 h intervals until 72h. The primary outcome was poor neurological outcome at 3 months after ROSC, defined as Glasgow?Pittsburgh cerebral performance categories 3 to 5. Result We enrolled 43 patients, and 21 had a poor neurologic outcome. NSE and S100B were significantly higher in the poor-outcome group at each time point. The the area under the receiver operating characteristic curves (AUROCs) of NSE and S100B were 0.91 / 0.95 immediately, 0.98 / 0.95 at 24 h, 0.99 / 1.00 at 48 h, and 0.94 / 1.00 at 72 h after ROSC, and no statistically significant differences were observed in AUROCs. The sensitivities, with a 0% false-positive rate (FPR) of NSE and S100B for poor neurological outcomes, were 66.7 / 47.6 immediately, 84.6 / 84.2 at 24 h, 88.9 / 100.0 at 48 h, and 93.3 (FPR, 10.0%) / 100.0 at 72 h. Conclusion High CSF NSE and S100B values are strong predictive markers of poor neurological outcome in OHCA survivors, even immediately after ROSC. In particular, CSF S100B showed higher sensitivities with a 0% FPR at 48 and 72 h after ROSC than those of CSF NSE. Further multicenter studies with large sample sizes are required to generalize our results.

Serum and Cerebrospinal Fluid Neuron-Specific Enolase for Diagnosis of Tuberculous Meningitis

송태진,김원주,최영철,이경열 연세대학교의과대학 2012 Yonsei medical journal Vol.53 No.6

Purpose: Late diagnosis and treatment lead to high mortality and poor prognosis in tuberculous meningitis (TbM). A rapid and accurate diagnosis is necessary for a good prognosis. Neuron-specific enolase (NSE) has been investigated as a biochemical marker of nervous tissue damage. In the present study, the usefulness of NSE was evaluated, and a cut-off value for the differential diagnosis of TbM was proposed. Materials and Methods: Patient charts were reviewed for levels of serum and cerebrospinal fluid (CSF) NSE, obtained from a diagnostic CSF study of samples in age- and gender-matched TbM (n=15), aseptic meningitis (n=28) and control (n=37) patients. Results: CSF/serum NSE ratio was higher in the TbM group than those of the control and aseptic groups (p=0.001). In binary logistic regression,CSF white blood cell count and CSF/serum NSE ratio were significant factors for diagnosis of TbM. When the cut-off value of the CSF/serum NSE ratio was 1.21, the sensitivity was 86.7% and the specificity was 75.4%. Conclusion: The CSF/serum NSE ratio could be a useful parameter for the early diagnosis of TbM. In addition, the authors of the present study suggest a cut-off value of 1.21 for CSF/serum NSE ratio.