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*

To determine expression levels of glial fibrillary acidic protein in patients of sepsis-associated encephalopathy (SAE) and its clinical significance.
 Methods: Patients, admitted to intensive care units and diagnosed as sepsis, were recruited to our study from October 2016 to August 2018 in the Third Xiangya Hospital, Central South University. SAE is defined as a brain dysfunction secondary to sepsis and without evidence of a primary central nervous system infection or encephalopathy due to other reasons. The SAE group and non-SAE group were classed by Confusion Assessment Method for the ICU (CAM-ICU) score. We measured the levels of serum GFAP, S100β and neuron-specific enolase (NSE) within 24 hours after diagnosis of sepsis, and compared the patients' general clinical data, ICU stay time, 28-day and 180-day mortality.
 Results: Among 152 enrolled patients, 58 and 94 were assigned to the SAE group and the non-SAE group, respectively. There were a significantly higher Sequential Organ Failure Assessment (SOFA) scores, 28-day mortality rate, as well as 180-day mortality rate in the SAE group (all P<0.001). The levels of GFAP, NSE and S100β in the SAE group were significantly higher than those in the non-SAE group (all P<0.001). The diagnostic values of GFAP was 0.67 μg/L, with sensitivity at 75.9% and specificity at 77.7%. Area under the receiver operating characteristic curve (AUROC) of GFAP, NSE and S100β were 0.803, 0.795 and 0.750, respectively. Pearson analysis showed that serum GFAP level was positively correlated with Acute Physiology and Chronic Health Evaluation II (APACHE II) score, but it was negatively correlated with Glasgow Coma Scale (GCS) score, 28-day survival rate and 180-day survival rate.
 Conclusion: The level of serum GFAP is significantly increased in SAE, which shows certain correlation with incidence, severity and prognosis of the disease.
APACHE ; Glial Fibrillary Acidic Protein ; blood ; Humans ; Intensive Care Units ; Organ Dysfunction Scores ; Prognosis ; ROC Curve ; Sepsis ; Sepsis-Associated Encephalopathy ; diagnosis

Neurological injury is a frequent and important complication of coronary artery bypass grafting (CABG). Several risk factors for this type of sequela have been identified, among them aortic arch atherosclerosis. Our previous study indicated that atherosclerotic burden in coronary arteries may likewise predict postoperative neurological complications (Pawliszak et al., 2016b). We assessed the severity of this condition by using the SYNTAX score calculator. However, diagnosing angiographic three-vessel coronary artery disease (3VD) could be an even simpler method of achieving this goal.
Aged ; Coronary Angiography ; Coronary Artery Bypass, Off-Pump/adverse effects* ; Coronary Artery Disease/surgery* ; Female ; Glial Fibrillary Acidic Protein/blood* ; Humans ; Male ; Middle Aged ; Neurofilament Proteins/blood* ; Neuropeptides/blood* ; Phosphorylation ; Prospective Studies ; Serpins/blood* ; Neuroserpin

Astroblastoma is an uncommon glial tumor with predominant manifestation in the young age. Herein, we report a case of 18-year-old astroblastoma female patient who presented with history of two months headache. Magnetic resonance imaging (MRI) of the brain demonstrated well circumscribed, intra-axial abnormal signal intensity lesion (size=5×4 cm²) in the right parieto-occipital region of the brain. The patient underwent complete surgical resection of the gross tumor, as confirmed by an early post-surgical MRI (i.e., within 24 hours of surgery). Histopathological examination revealed neoplastic lesion exhibiting perivascular pseudo-rosettes with centrally hyalinized blood vessel and focal nuclear pleomorphism. Immunohistochemistry staining illustrated reactivity for glial fibrillary acidic protein and integrase interactor 1 (INI-1). These features rendered the diagnosis of astroblastoma. A comprehensive review of the current literature to summarize the clinicopathological and radiological characteristics, prognostic factors and current treatment strategies of astroblastomas is also presented. Our study would expand the pool of this uncommon tumor towards its better understanding and optimal treatment.
Adolescent ; Blood Vessels ; Brain ; Brain Neoplasms ; Craniotomy ; Diagnosis ; Female* ; Glial Fibrillary Acidic Protein ; Headache ; Humans ; Hyalin ; Immunohistochemistry ; Integrases ; Magnetic Resonance Imaging ; Neoplasms, Neuroepithelial*

The cannabinoid (CB2) receptor type 2 has been proposed to prevent the degeneration of dopamine neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. However, the mechanisms underlying CB2 receptor-mediated neuroprotection in MPTP mice have not been elucidated. The mechanisms underlying CB2 receptor-mediated neuroprotection of dopamine neurons in the substantia nigra (SN) were evaluated in the MPTP mouse model of Parkinson's disease (PD) by immunohistochemical staining (tyrosine hydroxylase, macrophage Ag complex-1, glial fibrillary acidic protein, myeloperoxidase (MPO), and CD3 and CD68), real-time PCR and a fluorescein isothiocyanate-labeled albumin assay. Treatment with the selective CB2 receptor agonist JWH-133 (10 μg kg⁻¹, intraperitoneal (i.p.)) prevented MPTP-induced degeneration of dopamine neurons in the SN and of their fibers in the striatum. This JWH-133-mediated neuroprotection was associated with the suppression of blood-brain barrier (BBB) damage, astroglial MPO expression, infiltration of peripheral immune cells and production of inducible nitric oxide synthase, proinflammatory cytokines and chemokines by activated microglia. The effects of JWH-133 were mimicked by the non-selective cannabinoid receptor WIN55,212 (10 μg kg⁻¹, i.p.). The observed neuroprotection and inhibition of glial-mediated neurotoxic events were reversed upon treatment with the selective CB2 receptor antagonist AM630, confirming the involvement of the CB2 receptor. Our results suggest that targeting the cannabinoid system may be beneficial for the treatment of neurodegenerative diseases, such as PD, that are associated with glial activation, BBB disruption and peripheral immune cell infiltration.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine* ; Animals ; Blood-Brain Barrier ; Chemokines ; Cytokines ; Dopamine* ; Dopaminergic Neurons* ; Fluorescein ; Glial Fibrillary Acidic Protein ; Macrophages ; Mice ; Microglia ; Neurodegenerative Diseases ; Neuroprotection ; Nitric Oxide Synthase Type II ; Parkinson Disease* ; Peroxidase ; Real-Time Polymerase Chain Reaction ; Receptor, Cannabinoid, CB2* ; Receptors, Cannabinoid ; Substantia Nigra

OBJECTIVETo determine the changes of serum Tau protein, glial fibrillary acidic protein (GFAP), tumor necrosis factor alpha (TNF-α), and malonaldehyde (MDA) in rats after blast-related traumatic brain injury (BTBI) and to provide relative information for further studies on BTBI mechanism and seek specific biomarkers for BTBI.

METHODSNinety male Sprague-Dawley rats were randomly assigned into three groups: control group, moderate blast injury group, and severe blast injury group (n=30 for each). Rats in the moderate and severe blast injury groups were respectively exposed to corresponding levels of BTBI. After explosion, serum levels of Tau, GFAP, TNF-α, and MDA in each group were determined by Elisa assay at different time points after injury (8 h, 24 h, 3 d, and 6 d). The extent of brain damage was detected by Nissl staining and TUNEL assay.

RESULTSSerum levels of Tau and GFAP rapidly increased and reached the peak at 24 h after either moderate or severe blast injury. All the values were significantly higher than control group at all time points (P<0.05). Serum TNF-α level of both injury groups peaked at 8 h after BTBI and stayed significantly higher than control group at all time points (P<0.05). Serum MDA of two injury groups began to significantly increase at 3 d and the level stayed significantly higher than control group until 6 d (P<0.05). Moreover, unlike the other biomarkers, serum MDA of severe blast injury group was significantly higher than moderate blast injury group at 6 d (P<0.05).

CONCLUSIONThe changes of serum Tau, GFAP, and TNF-α showed a good sensitivity at the acute phase after BTBI (within 24 h). However, their specificity and correlation with the extent of injury were limited in this experiment. Moreover, although the change of serum MDA showed a poor sensitivity and specificity to the diagnosis of BTBI during the first few days, it can reflect the injury degree at 6 d after injury. Therefore, further studies are needed to improve the methods of detecting more serum markers and investigate the significance of multiple markers in diagnosing BTBI.

Animals ; Biomarkers ; blood ; Blast Injuries ; blood ; Brain Injuries ; blood ; Enzyme-Linked Immunosorbent Assay ; Glial Fibrillary Acidic Protein ; blood ; Male ; Malondialdehyde ; blood ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; analysis ; tau Proteins ; blood

OBJECTIVETo evaluate the effect of hypothermia therapy on serum glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) levels in neonates with hypoxic-ischemic encephalopathy (HIE).

METHODSSixty-four HIE neonates were enrolled in this study. Thirty-three neonates with mild HIE were given conventional treatment and 31 neonates with moderate or severe HIE received conventional treatment and hypothermia therapy. Serum levels of GFAP and UCH-L1 were measured using ELISA before treatment and 6-12 hours after treatment.

RESULTSSerum levels of IL-6, IL-8, GFAP and UCH-L1 in the moderate/severe HIE group were significantly higher than in the mild HIE group (P<0.05) before treatment. Serum GFAP level was positively correlated with serum IL-6 (r=0.54; P<0.05) and IL-8 levels (r=0.63; P<0.05), while negatively correlated with Apgar score (r=-0.47, P<0.05). After treatment, serum levels of IL-6, IL-8 and UCH-L1 in the moderate/severe HIE group were significantly reduced (P<0.05), while serum GFAP levels increased significantly (P<0.05). The patients with abnormal neurological development showed higher serum GFAP levels than those with favourable prognosis (P<0.05). Receiver operating characteristic (ROC) curves analysis demonstrated that the area under curve (AUC) of GFAP and UCH-L1 were 0.714 and 0.703 respectively. At a cut-off value of 0.07 ng/mL, the sensitivity and specificity of GFAP for the diagnosis of HIE were 77% and 78% respectively.

CONCLUSIONSHypothermia therapy can decrease serum UCH-L1 levels and increase serum GFAP levels in neonates with HIE. Based on their diagnostic value of brain injury, GFAP and UCH-L1 are promising to be novel biomarkers for HIE.

Biomarkers ; Female ; Glial Fibrillary Acidic Protein ; blood ; Humans ; Hypothermia, Induced ; Hypoxia-Ischemia, Brain ; blood ; therapy ; Infant, Newborn ; Male ; Ubiquitin Thiolesterase ; blood

OBJECTIVEThe finding of vasculogenic mimicry (VM) in many solid tumors indicates that tumor cells themselves could participate in the construction of tumor vessels. However the origin of these cells is still not fully elucidated, and whether these vessels have the ability of blood-supply is still unclear. Preliminary studies were performed to investigate whether part of tumor neovascularity is derived from tumor stem cells (TSCs) and whether TSCs-derived vessels are functional.

METHODSTransplanted glioma tissues obtained from subcutaneous and orthotopic transplantation nude mouse models were processed into paraffin sections. In order to identify the cell origin and types of tumor vessels, sections were stained with CD31, CD34, CD133, GFAP, Ki67 and HLA, respectively. CD34-PAS staining was performed as well. A part of tumor-bearing mice were perfused with activated carbon through the systemic circulation and the distribution of activated carbon was observed.

RESULTSCD34-PAS staining showed that endothelium-dependent vessels (CD34(+), PAS(+)), VM vessels (CD34(-), PAS(+)), and the MVs (CD34(+), PAS(-)) could be seen in the transplantated tumors. Activated carbon particles were observed in all three types of vessels. CD31(+) cells adherent to the luminal surface of vessel wall. CD34(+) cells distributed along the vessels as well, but morphologically were more like a transition type between tumor cells and endothelial cells. Human specific Ki67 and HLA positive cells could be seen in the tumor vessels indicating that these vessels were derived from human tumor cells. Moreover, cells of tumor vessels were proved to be constructed by human tumor cells mainly and fusion cells of host cells and tumor cells under confocal microscope.

CONCLUSIONSThree types of blood supply sources including endothelium-dependent vessels, vasculogenic mimicry (VMs) and mosaic vessels (MVs) exist in transplantation tumors of human glioma. Glioma stem and progenitor cells (GSCPs) have the potential to differentiate and transdifferentiate into VMs and MVs.

AC133 Antigen ; Animals ; Antigens, CD ; metabolism ; Antigens, CD34 ; metabolism ; Brain ; blood supply ; Brain Neoplasms ; blood supply ; metabolism ; pathology ; Carbon ; metabolism ; pharmacokinetics ; Cell Line, Tumor ; Endothelium, Vascular ; metabolism ; pathology ; Glial Fibrillary Acidic Protein ; metabolism ; Glioma ; blood supply ; metabolism ; pathology ; Glycoproteins ; metabolism ; HLA Antigens ; metabolism ; Humans ; Ki-67 Antigen ; metabolism ; Mice ; Mice, Nude ; Microcirculation ; Neoplasm Transplantation ; Neoplastic Stem Cells ; metabolism ; pathology ; Neovascularization, Pathologic ; metabolism ; pathology ; Peptides ; metabolism ; Periodic Acid-Schiff Reaction ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism

OBJECTIVETo investigate the protective effects of putative AGEs (advanced glycation endproducts) inhibitor salidroside against aging in an accelerated mouse aging model induced by D-galactose.

METHODSA group of 5-month-old C57BL/6J mice were treated daily with D-galactose, D-galactose combined with salidroside, salidroside alone, and control buffer for 8 weeks. At the end of the treatment, serum AGEs levels, neurological activities, expression of glial fibrillary acidic protein (GFAP) and neurotrophin-3 (NT-3) in the cerebral cortex, as well as lymphocyte proliferation and IL-2 production were determined.

RESULTSD-galactose induced mouse aging model was developed as described before. As expected, salidroside blocked D-galactose induced increase of serum AGEs levels. It also reversed D-galactose induced aging effects in neural and immune system, as evidenced by improving motor activity, increasing memory latency time, and enhancing lymphocyte mitogenesis and interleukin-2 (IL-2) production. Furthermore, elevated expression of GFAP and NT-3 in the aged model mice was also reduced upon salidroside treatment.

CONCLUSIONSalidroside inhibits AGEs formation in vivo, which at least partially contributes to its anti-aging effect in D-galactose induced aging model.

Aging, Premature ; blood ; chemically induced ; prevention & control ; Animals ; Cerebral Cortex ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Galactose ; Glial Fibrillary Acidic Protein ; Glucosides ; pharmacology ; therapeutic use ; Glycation End Products, Advanced ; blood ; Interleukin-2 ; metabolism ; Memory ; drug effects ; Mice ; Mice, Inbred C57BL ; Motor Activity ; drug effects ; Nerve Growth Factors ; metabolism ; Nerve Tissue Proteins ; metabolism ; Phenols ; pharmacology ; therapeutic use ; Spleen ; drug effects ; immunology ; T-Lymphocytes ; drug effects

OBJECTIVETo isolate, culture and identify glioma stem cells from human malignant glioma cell line U87, and investigate the changes of pro-angiogenic factors production by glioma stem cells followed by activation of CXCR4 and observe their tumorigenesis as well as the expression of vascular endothelial growth factor when implanted into nude mice.

METHODSThe ratio of CD133 positive cells was detected by flow cytometry. Magnetic separation of CD133 positive cells was carried out on the magnetic cell sorting system (MACS). Expression of nestin, glial fibrillary acidic protein (GFAP) and CXCR4 on tumorspheres was detected by indirect immunofluorescence under confocal laser scanning microscopy. The functional activation of CXCR4 was assessed by calcium mobilization experiments. ELISA was used to detect the production of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) in conditioned medium. Glioma stem cells were implanted into nude mice to assess their tumorigenesis ability and the expression of VEGF.

RESULTSThe ratio of CD133 positive cells with stem cell property was 0.5% in U87 cells. Activation of CXCR4 on glioma stem cells induced calcium mobilization and increased VEGF and IL-8 protein secretion. CD133 positive cells secreted more VEGF and IL-8 than their negative counterparts in vitro. Tumors derived from CD133 positive cells grew more rapidly and expressed elevated level of VEGF than their negative counterparts.

CONCLUSIONSThere are a small fraction of glioma stem cells in human glioblastoma cell line U87. Expressing functional CXCR4 and secreting more pro-angiogenic factors may be involved in tumor angiogenesis mediated by glioma stem cells.

AC133 Antigen ; Animals ; Antigens, CD ; analysis ; Brain Neoplasms ; blood supply ; metabolism ; pathology ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Glial Fibrillary Acidic Protein ; metabolism ; Glioblastoma ; blood supply ; metabolism ; pathology ; Glycoproteins ; analysis ; Humans ; Interleukin-8 ; metabolism ; Intermediate Filament Proteins ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Neoplastic Stem Cells ; metabolism ; transplantation ; Neovascularization, Pathologic ; Nerve Tissue Proteins ; metabolism ; Nestin ; Peptides ; analysis ; Receptors, CXCR4 ; genetics ; metabolism ; physiology ; Vascular Endothelial Growth Factor A ; metabolism