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

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.
Humans ; Biomarkers ; Brain Diseases/therapy* ; Carbon Monoxide Poisoning/therapy* ; Oxygen ; Phosphopyruvate Hydratase ; Prognosis ; S100 Calcium Binding Protein beta Subunit ; Transcranial Direct Current Stimulation

Objective: To explore the application value of bispectral index(BIS) , specific protein 100β(S100β) combined with Copeptinin patients with acute severe carbon monoxide poisoning (ASCMP). Methods: A total of 256 patients with acute carbon monoxide poisoning admitted to Hengshui People's Hospital from June 2018 to June 2020 were collected, and they were divided into 30 mild cases, 40 moderate cases and 186 severe cases according to the degree of poisoning. Among them, patients with severe carbon monoxide poisoning were divided into a poor prognosis group (20 cases) and a good prognosis group (166 cases) according to whether adverse events occurred. The changes of creatine kinase isoenzyme (CK-MB) , N-terminal precursor B-type brain natriuretic peptide (NT-proBNP) , BIS, S100β, and Copeptin in poisoned patients were measured. Logistic regression analysis and receiver operating characteristic (ROC) curve were used to evaluate the significance of relevant indicators for ASCMP patients. Results: Compared with the mild-to-moderate group, CK-MB, NT-proBNP, S100β, Copeptin increased, and BIS value decreased in the severe group (P< 0.05). 24 hours after admission, compared with the good prognosis group, CK-MB, NT-proBNP, S100β, Copeptin in the poor prognosis group increased, and the BIS value decreased (P<0.05). In the poor prognosis group, CK-MB, NT-proBNP, S100β, and Copeptin at 72 hours after admission were all lower than those at 24 hours after admission, and the BIS value was higher than that at 24 hours after admission (P<0.05). Logistic regression analysis showed that ASCMP patients with increased S100β, Copeptin, and decreased BIS values had an increased risk of adverse events (P<0.05). The ROC curve showed that the area under the curve of the combined detection of BIS, S100β and Copeptin was 0.859, which had a great predictive value for the prognosis of ASCMP patients. Conclusion: BIS, S100β combined with Copeptin detection is of great value for early assessment of ASCMP disease and prognosis prediction.
Biomarkers ; Carbon Monoxide Poisoning ; Creatine Kinase, MB Form ; Humans ; Natriuretic Peptide, Brain ; Peptide Fragments ; Prognosis ; ROC Curve ; S100 Calcium Binding Protein beta Subunit

To investigate the association between chronic unpredictable mild stress (CUMS)-induced depressive-like behavior in rats and expressions of brain-derived neurotrophic factor (BDNF) and S100β in the hippocampal and prefrontal cortex. Rats were randomly assigned to three groups:saline control group,saline+CUMS group,and citalopram +CUMS group. CUMS was used for depression modeling in rats. Depressive-like behavior in rats were evaluated by open-field test,sucrose preference test,and novel object recognition test. S100β and BDNF expressions were tested by enzyme-linked immunosorbent assay. Rats in the saline+CUMS group had significantly lower score in sucrose preference [(52.48±13.14)%],basic motor tasks [(845.8±371.4)s],fine motor tasks [(565.6±211.9)s],and longer resting time [(282.6±11.8)s] compared to the control group [(84.30±6.15)% (=7.49,=0.000),(1239.1±281.6)s (=2.83,=0.008),(801.8±150.9)s (=3.05,=0.003),(268.2±12.8)s (=2.72,=0.001)]. Compared with the citalopram+CUMS group,rats from the saline+CUMS group also showed significantly lower results in sucrose preference [(80.55±11.31)%,=5.39,=0.000],basic motor tasks [(1156.4±314.7)s,=2.13,=0.031],and fine motor tasks [(736.1±150.0)s,=2.21,=0.008]. There were no significant differences in the expression of hippocampal and prefrontal BDNF between these two groups,but rats from the saline+CUMS group expressed significantly higher levels of S100β compared to rats from the citalopram+CUMS group [(13.22±2.23) ng/g (10.55±2.72) ng/g,=2.67,=0.014]. Pearson correlation analysis revealed that the expression of S100β was positively correlated with the expression of BDNF in the prefrontal cortex and hippocampus (=0.35,=0.034;=0.36,=0.034).The novel object recognition index was positively correlated with the expression of BDNF in the hippocampus(=0.38,=0.021),and the duration of fine-motor activities was negatively correlated with S100β in the prefrontal cortex (=-0.36,=0.037). Different types of depressive behaviors in rats induced by CUMS are associated with the selective expression of S100β and BDNF in two different brain cortex. S100β protein and BDNF may independently participate in the pathogenesis of depression.
Animals ; Antidepressive Agents ; Brain-Derived Neurotrophic Factor ; metabolism ; Citalopram ; Depression ; metabolism ; Disease Models, Animal ; Frontal Lobe ; metabolism ; Hippocampus ; metabolism ; Random Allocation ; Rats ; S100 Calcium Binding Protein beta Subunit ; metabolism ; Stress, Psychological

OBJECTIVE: To explore the protective effect of SBi4211 (heptamidine), an inhibitor of S100B, against central nervous system injury induced by HIV-1 envelope protein gp120. METHODS: In an RESULTS: In the cell co-culture system, SBi4211 treatment significantly inhibited gp120-induced expression of S100B, RAGE and GFAP in U251 cells ( CONCLUSIONS SBi4211 can protect neurons from gp120-induced neurotoxicity possibly by inhibiting the S100B/ RAGE-mediated signaling pathway.
Animals ; Astrocytes ; Blotting, Western ; Central Nervous System ; HIV Envelope Protein gp120 ; Mice ; Neurons ; S100 Calcium Binding Protein beta Subunit ; Signal Transduction

Major depressive disorder (MDD) is the most common nonfatal disease burden worldwide. Systemic chronic low-grade inflammation has been reported to be associated with MDD progression by affecting monoaminergic and glutamatergic neurotransmission. However, whether various proinflammatory cytokines are abnormally elevated before the first episode of depression is still largely unclear. Here, we evaluated 184 adolescent patients who were experiencing their first episode of depressive disorder, and the same number of healthy individuals was included as controls. We tested the serum levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), IgE, 14 different types of food antigen-specific IgG, histamine, homocysteine, S100 calcium-binding protein B, and diamine oxidase. We were not able to find any significant differences in the serum levels of hs-CRP or TNF-α between the two groups. However, the histamine level of the patients (12.35 μM) was significantly higher than that of the controls (9.73 μM, P < 0.001, Mann-Whitney U test). Moreover, significantly higher serum food antigen-specific IgG positive rates were also found in the patient group. Furthermore, over 80% of patients exhibited prolonged food intolerance with elevated levels of serum histamine, leading to hyperpermeability of the blood-brain barrier, which has previously been implicated in the pathogenesis of MDD. Hence, prolonged high levels of serum histamine could be a risk factor for depressive disorders, and antihistamine release might represent a novel therapeutic strategy for depression treatment.
Adolescent ; Biomarkers ; blood ; C-Reactive Protein ; Chronic Disease ; Cytokines ; Depressive Disorder, Major ; blood ; epidemiology ; etiology ; Female ; Food Hypersensitivity ; blood ; complications ; Histamine ; blood ; Homocysteine ; blood ; Humans ; Immunoglobulin E ; blood ; Immunoglobulin G ; blood ; immunology ; Inflammation Mediators ; blood ; Male ; Risk Factors ; S100 Calcium Binding Protein beta Subunit ; blood ; Young Adult

While the survival rate of preterm infants has continually increased with the development of perinatal and neonatal monitoring techniques, the incidence of brain injury in preterm infants has been increasing, resulting in varying degrees of cognitive impairment and movement disorders. Measuring the biomarkers of brain damage is an important means to diagnose brain injury. The biomarkers can be divided into neuroglial damage markers, neuronal damage markers and other markers according to the features of injured cells. The biomarkers widely used in clinical practice include S100B protein, myelin basic protein and neuron-specific enolase. Recent studies have newly discovered a collection of markers that can suggest potential brain injury in preterm infants, such as glial fibrillary acidic protein, neurofilament light chain protein, α-II spectrin breakdown products, chemokines, melatonin and urinary metabolomics. These biomarkers can contribute to the early diagnosis and treatment of preterm brain injury, essential for improving neural development and prognosis. This article reviews the latest research advances in the biomarkers of preterm brain injury, in order to provide evidence for the early diagnosis and treatment of this condition.
Biomarkers ; Brain ; Brain Injuries ; Female ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Pregnancy ; S100 Calcium Binding Protein beta Subunit

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 association between rs9722 polymorphisms in the S100B gene and hand, foot and mouth disease (HFMD) caused by enterovirus 71.

METHODSA total of 124 HFMD children with enterovirus 71 infection were enrolled as subjects, and 56 healthy children were enrolled as control group. The rs9722 polymorphisms in the S100B gene were detected for both groups, and the serum level of S100B protein was measured for 74 HFMD children.

RESULTSThe rs9722 locus of the S100B gene had three genotypes, CC, CT, and TT, and the genotype frequencies were in accordance with Hardy-Weinberg equilibrium. Compared with the control group, the HFMD group had significant increases in the frequencies of TT genotype and T allele (P<0.01). Children with severe HFMD caused by enterovirus 71 infection had significantly higher frequencies of TT genotype and T allele than those with moderate or mild HFMD (P<0.05). Compared with the cured patients, the patients with poor prognosis had significant increases in the frequencies of TT genotype and T allele in the rs9722 locus of the S100B gene (P<0.05). Among the 74 children with HFMD, the children with TT genotype had the highest serum level of S100B protein, and those with CC genotype had the lowest level (P<0.01).

CONCLUSIONST allele in the rs9722 locus of the S100B gene might be a risk factor for severe HFMD caused by enterovirus 71 infection.

Child, Preschool ; Enterovirus A, Human ; Enterovirus Infections ; complications ; Female ; Genotype ; Hand, Foot and Mouth Disease ; etiology ; genetics ; Humans ; Infant ; Male ; Polymorphism, Genetic ; S100 Calcium Binding Protein beta Subunit ; genetics