Neurological diseases are a major health concern, and brain injury is a typical pathological process in various neurological disorders. Different biomarkers in the blood or the cerebrospinal fluid are associated with specific physiological and pathological processes. They are vital in identifying, diagnosing, and treating brain injuries. In this review, we described biomarkers for neuronal cell body injury (neuron-specific enolase, ubiquitin C-terminal hydrolase-L1, αII-spectrin), axonal injury (neurofilament proteins, tau), astrocyte injury (S100β, glial fibrillary acidic protein), demyelination (myelin basic protein), autoantibodies, and other emerging biomarkers (extracellular vesicles, microRNAs). We aimed to summarize the applications of these biomarkers and their related interests and limits in the diagnosis and prognosis for neurological diseases, including traumatic brain injury, status epilepticus, stroke, Alzheimer's disease, and infection. In addition, a reasonable outlook for brain injury biomarkers as ideal detection tools for neurological diseases is presented.
Humans ; Biomarkers/cerebrospinal fluid* ; Nervous System Diseases/diagnosis* ; Brain Injuries/metabolism* ; Phosphopyruvate Hydratase/cerebrospinal fluid* ; Glial Fibrillary Acidic Protein/blood* ; S100 Calcium Binding Protein beta Subunit/blood* ; tau Proteins/cerebrospinal fluid* ; Ubiquitin Thiolesterase/blood* ; Myelin Basic Protein/cerebrospinal fluid* ; Neurofilament Proteins/blood* ; MicroRNAs/blood* ; Brain Injuries, Traumatic/metabolism*

OBJECTIVE: To investigate the mechanism of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSC) in alleviating brain injury after resuscitation in swine with cardiac arrest (CA). METHODS: Twenty-nine healthy male large white swine were randomly divided into Sham group (n = 9), cardiopulmonary resuscitation (CPR) group (n = 10) and hESC-MSC group (n = 10). The Sham group only completed animal preparation. In CPR group and hESC-MSC group, the swine model of CA-CPR was established by inducing ventricular fibrillation for 10 minutes with electrical stimulation and CPR for 6 minutes. At 5 minutes after successful resuscitation, hESC-MSC 2.5×10⁶/kg was injected via intravenous micropump within 1 hour in hESC-MSC group. Venous blood samples were collected before resuscitation and at 4, 8, 24, 48 and 72 hours of resuscitation. The levels of neuron specific enolase (NSE) and S100B protein (S100B) were detected by enzyme linked immunosorbent assay (ELISA). At 24, 48 and 72 hours of resuscitation, neurological deficit score (NDS) and cerebral performance category (CPC) were used to evaluate the neurological function of the animals. Three animals from each group were randomly selected and euthanized at 24, 48, and 72 hours of resuscitation, and the hippocampus tissues were quickly obtained. Immunofluorescence staining was used to detect the distribution of hESC-MSC in hippocampus. Immunohistochemical staining was used to detect the activation of astrocytes and microglia and the survival of neurons in the hippocampus. The degree of apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). RESULTS: The serum NSE and S100B levels of brain injury markers in CPR group and hESC-MSC group were significantly higher than those in Sham group at 24 hours of resuscitation, and then gradually increased. The levels of NSE and S100B in serum at each time of resuscitation in hESC-MSC group were significantly lower than those in CPR group [NSE (μg/L): 20.69±3.62 vs. 28.95±3.48 at 4 hours, 27.04±5.56 vs. 48.59±9.22 at 72 hours; S100B (μg/L): 2.29±0.39 vs. 3.60±0.73 at 4 hours, 2.38±0.15 vs. 3.92±0.50 at 72 hours, all P < 0.05]. In terms of neurological function, compared with the Sham group, the NDS score and CPC score in the CPR group and hESC-MSC group increased significantly at 24 hours of resuscitation, and then gradually decreased. The NDS and CPC scores of hESC-MSC group were significantly lower than those of CPR group at 24 hours of resuscitation (NDS: 111.67±20.21 vs. 170.00±21.79, CPC: 2.33±0.29 vs. 3.00±0.00, both P < 0.05). The expression of hESC-MSC positive markers CD73, CD90 and CD105 in the hippocampus of hESC-MSC group at 24, 48 and 72 hours of resuscitation was observed under fluorescence microscope, indicating that hESC-MSC could homing to the damaged hippocampus. In addition, compared with Sham group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of CPR group were significantly increased, and the proportion of neurons was significantly decreased at 24, 48 and 72 hours of resuscitation. Compared with CPR group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of hESC-MSC group decreased and the proportion of neurons increased significantly at 24 hours of resuscitation [proportion of astrocytes: (14.33±1.00)% vs. (30.78±2.69)%, proportion of microglia: (12.00±0.88)% vs. (27.89±5.68)%, apoptotic index: (12.89±3.86)% vs. (52.33±7.77)%, proportion of neurons: (39.44±3.72)% vs. (28.33±1.53)%, all P < 0.05]. CONCLUSIONS Application of hESC-MSC at the early stage of resuscitation can reduce the brain injury and neurological dysfunction after resuscitation in swine with CA. The mechanism may be related to the inhibition of immune cell activation, reduction of cell apoptosis and promotion of neuronal survival.
Animals ; Heart Arrest/therapy* ; Cardiopulmonary Resuscitation ; Swine ; Humans ; Male ; Human Embryonic Stem Cells/cytology* ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology* ; Phosphopyruvate Hydratase/blood* ; Brain Injuries/therapy* ; S100 Calcium Binding Protein beta Subunit ; Apoptosis ; Disease Models, Animal

To study the effect of modified Buyang Huanwu Decoction on the hemorrhagic transformation after intravenous thrombolysis of recombinant tissue type plasminogen activator(rt-PA) in patients with super early(onset time<4. 5 h) cerebral infarction. From March 2016 to July 2018,at the brain disease zone of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,212 cases of super early cerebral infarction were selected and divided into two group according to the randomized complete blocks designs: control group(106 cases) and traditional Chinese medicine group(106 cases). The control group was treated with rt-PA intravenous thrombolysis,while the traditional Chinese medicine group was treated with modified Buyang Huanwu Decoction in addition to the therapy of the control group. Both groups were treated for 14 days. Neurological deficit score,serum matrix metalloproteinase-9(MMP-9),neuron specific enolase(NSE),vascular endothelial growth factor(VEGF) and plasma cellular fibronectin(c-FN) levels,the incidence of hemorrhagic transformation,clinical efficacy and adverse drug reactions before and after treatment were compared between the two groups. According to the findings,at the 14 thday after treatment,the rank sum test of the grade data showed that the clinical efficacy of the traditional Chinese medicine group was better than that of the control group(Z =-2. 033,P = 0. 042); on the basis of χ2 test,the total efficiency of the traditional Chinese medicine group was higher than that of the control group(χ2= 4. 895,P =0. 027); the hemorrhagic transformation rate of the traditional Chinese medicine group was lower than that of the control group within14 days of treatment(χ2= 3. 962,P = 0. 047). MMP-9 levels in the traditional Chinese medicine group were lower than those in the control group at the 3 rd,5 th,7 th,10 th,14 thd after treatment(t =-2. 474,-3. 022,-5. 163,-6. 998,-9. 821; P = 0. 014,0. 003,0,0,0). The improvement of c-FN,NSE,VEGF and NIHSS scores in the traditional Chinese medicine group was superior to that of the control group after 14 days of treatment(t =-2. 343,-3. 187,-2. 129,-3. 105; P = 0. 020,0. 002,0. 034,0. 002). No obvious adverse reactions of modified Buyang Huanwu Decoction were observed during 14 days of treatment. Modified Buyang Huanwu Decoction could reduce the expressions of MMP-9,c-FN,NSE and VEGF after rt-PA intravenous thrombolysis in patients with super early cerebral infarction,and decrease the hemorrhagic transformation rate after thrombolysis,with high safety.
Cerebral Infarction ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Fibronectins ; blood ; Humans ; Matrix Metalloproteinase 9 ; blood ; Medicine, Chinese Traditional ; Phosphopyruvate Hydratase ; blood ; Recombinant Proteins ; therapeutic use ; Thrombolytic Therapy ; Tissue Plasminogen Activator ; therapeutic use ; Vascular Endothelial Growth Factor A ; blood

OBJECTIVE: To study the clinical value of serum neuroglobin in evaluating hypoglycemic brain injury in neonates. METHODS: A total of 100 neonates with hypoglycemia were enrolled as subjects. According to amplitude-integrated EEG (aEEG) findings and/or clinical manifestations, they were divided into symptomatic hypoglycemic brain injury group (n=22), asymptomatic hypoglycemic brain injury group (n=37) and hypoglycemic non-brain injury group (n=41). The three groups were compared in terms of blood glucose, duration of hypoglycemia, levels of neuroglobin and neuron-specific enolase (NSE), and modified aEEG score. The correlation of neuroglobin with NSE and modified aEEG score was analyzed. The receiver operating characteristic (ROC) curve was plotted. RESULTS: Compared with the asymptomatic hypoglycemic brain injury and hypoglycemic non-brain injury groups, the symptomatic hypoglycemic brain injury group had significantly lower blood glucose and modified aEEG score, significantly higher neuroglobin and NSE levels, and a significantly longer duration of hypoglycemia (P<0.05). Compared with the hypoglycemic non-brain injury group, the asymptomatic hypoglycemic brain injury group had significantly lower blood glucose and modified aEEG score, significantly higher neuroglobin and NSE levels, and a significantly longer duration of hypoglycemia (P<0.05). Neuroglobin was positively correlated with NSE and duration of hypoglycemia (r=0.922 and 0.929 respectively; P<0.05) and negatively correlated with blood glucose and modified aEEG score (r=-0.849 and -0.968 respectively; P<0.05). The areas under the ROC curve of neuroglobin, NSE and modified aEEG score were 0.894, 0.890 and 0.941 respectively, and neuroglobin had a sensitivity of 80.8% and a specificity of 95.8% at the optimal cut-off value of 108 mg/L. CONCLUSIONS Like NSE and modified aEEG score, serum neuroglobin can also be used as a specific indicator for the assessment of brain injury in neonates with hypoglycemia and has a certain value in clinical practice.
Brain Injuries ; Electroencephalography ; Humans ; Hypoglycemic Agents ; Infant, Newborn ; Neuroglobin ; blood ; Phosphopyruvate Hydratase

PURPOSE: Mild traumatic brain injury (TBI) is common but accurate diagnosis and its clinical consequences have been a problem. Maxillofacial trauma does have an association with TBI. Neuron-specific enolase (NSE) has been developed to evaluate neuronal damage. The objective of this study was to investigate the accuracy of NSE serum levels to detect mild brain injury of patients with sustained maxillofacial fractures during motor vehicle accidents. METHODS: Blood samples were drawn from 40 healthy people (control group) and 48 trauma patients who had sustained isolated maxillofacial fractures and mild brain injury in motor vehicle accidents. Brain injuries were graded by Glasgow Coma Scale. In the trauma group, correlations between the NSE serum value and different facial fracture sites were also assessed. RESULTS: The NSE serum level (mean ± SD, ng/ml) in the 48 patients with maxillofacial fractures and mild TBI was 13.12 ± 9.68, significantly higher than that measured in the healthy control group (7.72 ± 1.82, p < 0.001). The mean NSE serum level (ng/ml) in the lower part of the facial skeleton (15.44 with SD 15.34) was higher than that in the upper facial part (12.42 with SD 7.68); and the mean NSE level (ng/ml) in the middle-and lower part (11.97 with SD 5.63) was higher than in the middle part (7.88 with SD 2.64). CONCLUSION An increase in NSE serum levels can be observed in patients sustained maxillofacial fractures and mild brain injury.
Accidents, Traffic ; Adult ; Aged ; Biomarkers ; blood ; Brain Injuries, Traumatic ; diagnosis ; Craniocerebral Trauma ; Female ; Humans ; Male ; Maxillary Fractures ; Maxillofacial Injuries ; Mesencephalon ; injuries ; Middle Aged ; Motorcycles ; Phosphopyruvate Hydratase ; blood ; Predictive Value of Tests ; Young Adult

Gastroenteropancreatic neuroendocrine neoplam (GEP-NEN) is a rare group of tumors with its incidence rising significantly in recent decades. Because of the late presentation of the disease and limitations in conventional biomarkers, about 50% of GEP-NEN patients manifests advanced disease when diagnosed. Therefore, it is vital to identify circulating biomarkers which can not only be used for early diagnosis but also accurately evaluating the biological behavior of GEP-NEN. This review summarizes the advances of circulating biomarkers in diagnosing and evaluating efficacy of treatment in GEP-NEN. Well-known circulating biomarkers include chromogranin A (CgA), pancreastatin (PST), chromogranin B (CgB), neuron-specific enolase (NSE) and pancreatic peptide(PP). Novel biomarkers including circulating tumor cell(CTC), microRNA and NETest are promising biomarkers with potential clinical benefit, but further researches are needed before their clinical applications.
Biomarkers, Tumor ; blood ; Chromogranin A ; blood ; Chromogranin B ; blood ; chemistry ; Gastrointestinal Neoplasms ; blood ; chemistry ; diagnosis ; genetics ; Humans ; MicroRNAs ; blood ; Neoplastic Cells, Circulating ; Neuroendocrine Tumors ; blood ; chemistry ; diagnosis ; genetics ; Pancreatic Neoplasms ; blood ; chemistry ; diagnosis ; genetics ; Pancreatic Polypeptide ; blood ; Phosphopyruvate Hydratase ; blood

OBJECTIVETo screen out retinoblastoma (RB)-related serum tumor markers by measuring the levels of serum alpha fetoprotein (AFP), carcino-embryonic antigen (CEA), neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724) in children with RB.

METHODSThe levels of seven serum tumor markers (AFP, CEA, NSE, CA125, CA153, CA199, and CA724) were determined in 20 children with RB and 20 healthy children (control) using a chemiluminescent immunoassay.

RESULTSThe serum levels and positive rates of NSE, CA153, and CA199 in the RB group were significantly higher than those in the control group (P<0.05). However, there were no significant differences in the levels of AFP, CEA, CA125, and CA724 between the two groups (P>0.05). NSE had the highest sensitivity, but a relatively low specificity for the diagnosis of RB. CA153 and CA199 had a relatively high specificity, but a relatively low sensitivity for the diagnosis of RB.

CONCLUSIONSThe serum levels and positive rates of NSE, CA153, and CA199 are high in children with RB. Combined measurement of these three serum tumor markers may have an important diagnostic value for RB.

Antigens, Tumor-Associated, Carbohydrate ; blood ; Biomarkers, Tumor ; blood ; CA-125 Antigen ; blood ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Phosphopyruvate Hydratase ; blood ; Retinal Neoplasms ; blood ; diagnosis ; Retinoblastoma ; blood ; diagnosis

OBJECTIVETo study the value of serum S100B protein and neuron-specific enolase (NSE) levels in predicting the severity of hand, foot and mouth disease (HFMD).

METHODSNinety children with HFMD were classified into three groups: common type, severe type, and critical type (n=30 each). Thirty healthy children were randomly selected as the control group. ELISA was used to measure serum levels of S100B protein and NSE before and at 7 days after treatment. The receiver operating characteristic (ROC) curve was used to evaluate the prediction efficiency of S100B protein and NSE for the severity of HFMD.

RESULTSThe critical type group had significant increases in the serum levels of S100B protein and NSE compared with the other three groups (P<0.01). The severe type group had significant increases in serum levels of S100B protein and NSE compared with the common type and control groups (P<0.01). The critical type and severe type groups had significant reductions in serum levels of S100B protein and NSE after treatment (P<0.05). Serum S100B protein had the highest Youden value of 0.611 at the cut-off value of 0.445 μg/L, with a sensitivity of 61% and a specificity of 100%, in the prediction of serious HFMD (including severe type and critical type HFMD). Serum NSE had the highest Youden value of 0.533 at the cut-off value of 5.905 μg/L, with a sensitivity of 80% and a specificity of 73%, in the prediction of serious HFMD. Combined measurements of these two parameters had a sensitivity of 86% and a specificity of 73% and had the highest predictive value for serious HFMD.

CONCLUSIONSThe serum levels of S100B protein and NSE help to predict the severity and treatment outcomes of HFMD. Combined measurements of these two parameters has a higher predictive value for serious HFMD.

Child ; Child, Preschool ; Female ; Hand, Foot and Mouth Disease ; blood ; Humans ; Male ; Phosphopyruvate Hydratase ; blood ; S100 Calcium Binding Protein beta Subunit ; blood

OBJECTIVETo investigate the protective effects of high-dose ulinastatin on the vital organs in patients undergoing total arch replacement for type A aortic dissection.

METHODSBetween September 2014 and March 2016, 66 patients with type A aortic dissection underwent total arch replacement at our center. Thirty-six of the patients received ulinastatin treatment at 300 000 U/8 h from admission to 3 days postoperatively and at 300 000 U/2 h during cardiopulmonary bypass surgery (UTI group), and the other 30 patients did not receive perioperative ulinastatin treatment (control group). The surgical data and blood biochemistry profiles on days 1, 3, and 5 postoperatively were compared between the two groups, and the postoperative ICU stay, re-operation for bleeding, ventilation for over 7 days, ultrafiltration for postoperative renal failure, tracheotomy, incidences of pulmonary and neurological complications and hospital death were also compared.

RESULTSs The operating time, cardiopulmonary bypass time, ACP time, cardiac arrest time, the lowest rectal temperature and frequency of bilateral and unilateral antegrade selective cerebral perfusion were similar between the two groups (P>0.05). Compared with those in the control group, patients in UTI group had lower lactate, S-100 and neuron specific enolase levels on the first postoperative day and higher OI on the 1st, 3rd, and 5th postoperative days (P<0.05), but serum creatinine, blood urea nitrogen, total bilirubin, and alanine aminotransferase levels were comparable between the two groups (P>0.05). No significant differences were found in the frequency of re-operation for bleeding, ultrafiltration for renal failure, tracheotomy, neurological complications or hospital death after the operation between the two groups, but the patients in UTI group had a shorter ICU time, a less frequent long-term ventilation and a lower incidence of pulmonary infection (P<0.05).

CONCLUSIONHigh-dose ulinastatin offers protection on pulmonary function and lowers the specific brain injury markers in patients with type A aortic dissection after total arch replacement, but its protective effects on brain is uncertain.

Aneurysm, Dissecting ; surgery ; Aorta, Thoracic ; surgery ; Aortic Aneurysm, Thoracic ; surgery ; Body Temperature ; Brain ; drug effects ; Cardiopulmonary Bypass ; Cerebrovascular Circulation ; Glycoproteins ; therapeutic use ; Humans ; Incidence ; Lactic Acid ; blood ; Lung ; drug effects ; Perfusion ; Phosphopyruvate Hydratase ; blood ; Postoperative Period ; Protective Agents ; therapeutic use ; S100 Proteins ; blood ; Time Factors

OBJECTIVETo explore the effect of Scalp acupuncture on serum neuron specific enolase (NSE) and S-100β concentrations, and incidence rates of postoperative delirium (POD) and postoperative cognitive function (POCD) of elderly patients undergoing hip replacement.

METHODSEighty-four patients undergoing scheduled hip replacement under combined spinal-epidural anesthesia (CSEA) were assigned to the control group (group C) and the scalp acupuncture group (group S) according to random digit table, 42 cases in each group. In group S, scalp acupuncture was additionally performed according to International Standardized Scheme for Scalp Acupuncture. Scalp acupuncture was performed during the operation from the MS1 middle line of forehead [1 cun before Shenting (GV24), including Shenting (GV24)] and MS5 middle line of vertex [from Baihui (DU20) to Qianding (DU21), including Baihui (DU20) and Qianding (DU21)]. The operation time and post-operative length of stay were observed. The midazolam dosage, hemorrhage amount, fluid transfusion amount, urine amount, use rates of ephedrine and atropine during the operation were also observed and compared between the two groups. The occurrence rate of POD and POCD at post-operative day 3 (T₁), week 1 (T₂), month 3 (T₃), and month 6 (T₄) were measured. Eighteen patients were randomly selected to collect blood from internal jugular vein before anesthesia t₀), immediately after ending the surgery (t₁), 6 h after operation (t₂), 24 h after operation (t₃), and 48 h after operation (t₄), respectively. Serum levels of NSE and S-100β were correspondingly measured.

RESULTSThere was no statistical difference in the operation time, midazolam dosage used during the operation, hemorrhage amount, fluid transfusion amount, urine amount, use rates of ephedrine and atropine (P > 0.05). Compared with group C, the post-operative length of stay was shortened in group S (P < 0.05). The incidence rate of POD and that of POCD at each time point were lower in group S (P < 0.05). The expression level of NSE decreased at t₂, t3, and t₄, and the expression level of S100β also decreased at t₁, t₂, t₃, and t₄(P < 0.05). There was no statistical difference in expression levels of NSE or S100β between the two groups at other time points (P > 0.05).

CONCLUSIONScalp acupuncture could attenuate central nervous system lesion and improve POCD of elderly patients undergoing hip replacement.

Acupuncture Points ; Acupuncture Therapy ; Aged ; Arthroplasty, Replacement, Hip ; Cognition ; Humans ; Length of Stay ; Phosphopyruvate Hydratase ; blood ; Postoperative Complications ; Postoperative Period ; S100 Calcium Binding Protein beta Subunit ; blood ; Scalp