A total of 47 glial tumors of the brain was studied for the demonstration of glial fibrillary acidic protein(GFA) in tumor cells. This study was primarily aimed to confirm the applicability in the differential diagnosis of various glial tumors occuring in central nervous system. Intracellular positivity was observed only in well differentiated and moderately differentiated astrocytoma cells. GFA was negative in primitive glioma and oligodendroglioma. In glioblastoma multiforme pleomorphic cells were positive for GFA while spindle cells were negative. Elongated ependymoma cells arranged particularly around blood vessels were moderately positive for GFA while most cuboidal cells and round cells were negative. GFA was most helpful for the diagnosis of mixed glioma, where a sharp distinction could be made among different cellular component based on GFA staining. In conclusion it was confirmed that GFA is very useful tool for the diagnosis of different glial tumors of central nervous system.
Astrocytoma ; Blood Vessels ; Brain* ; Central Nervous System ; Diagnosis ; Diagnosis, Differential ; Ependymoma ; Glial Fibrillary Acidic Protein* ; Glioblastoma ; Glioma ; Oligodendroglioma

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

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*

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

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

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

PURPOSE: An experimental study was carried out to evaluate the morphological changes in the blood brain barrier and neighbouring brain tissue caused by Gd-DTPA in uremia-induced rabbits. MATERIALS AND METHODS: Bilateral renal arteries and veins of ten rabbits were ligated. Gd-DTPA(0.2 mmol/kg) was intravenously injectedinto seven rabbits immediately after ligation. After MRI, they were sacrificed 2 or 3 days after ligation in orderto observe light and electron microscopic changes in the blood brain barrier and brain tissue. RESULTS: MRIfindings were normal, except for enhancement of the superior and inferior sagittal sinuses on T1 weighted imagesin uremia-induced rabbits injected with Gd-DTPA. On light microscopic examination, these rabbits showed perivascular edema and glial fibrillary acidic protein expression ; electron microscopic examination showed separation of tight junctions of endothelial cells, duplication/rarefaction of basal lamina, increased lysosomes of neurons with neuronal death, demyelination of myelin, and extravasation of red blood cells. Uremia-induced rabbits injected with Gd-DTPA showed more severe changes than those without Gd-DTPA injection. CONCLUSION: Injuries to the blood brain barrier and neighbouring brain tissue were aggravated by Gd-DTPA administration inuremia-induced rabbits. These findings appear to be associated with the neurotoxicity of Gd-DTPA.
Animals ; Basement Membrane ; Blood-Brain Barrier* ; Brain Injuries ; Brain* ; Demyelinating Diseases ; Edema ; Endothelial Cells ; Erythrocytes ; Gadolinium DTPA* ; Glial Fibrillary Acidic Protein ; Ligation ; Magnetic Resonance Imaging ; Myelin Sheath ; Neurons ; Rabbits* ; Renal Artery ; Tight Junctions ; Veins

AIMA method of coculture of brain capillary endothelial cells (BCECs) and astrocytes of rats was used to evaluate nanoparticle's blood-brain barrier (BBB) transcytosis and toxicity at the endothelial tight junction.

METHODSA lipophilic fluorescent probe, 6-coumarin, was incorporated in poly (ethyleneglycol)-poly (lactide) nanoparticle using double emulsion/solvent evaporation method. BCECs and astrocytes were firstly isolated from brain of newborn rats and characterized by their morphology and immunocytochemistry staining, separately. Subsequently, a coculture model with BCECs on the top of micro-porous membrane of cell culture insert and astrocytes on the bottom side was established. The permeability of 14C-labeled sucrose and nanoparticle were determined, separately.

RESULTSThe mean weight-based diameter of 6-coumarin loaded nanoparticles was (102.4 +/- 6.8) nm, with zeta potential of (-16.81 +/- 1.05) mV. BCECs were positive for factor VIII staining and glial fibrillary acidic protein was expressed in astrocytes. The transendothelial electrical resistance reached up to (313 +/- 23) omega x cm2. The tight junction between BCECs in the coculture model could be visualized by both scanning electron microscopy and transmission electron microscopy. The unchanged paracellular transport of sucrose proved that nanoparticle with concentration lower than 200 microg x mL(-1) did not impact the integrity of BBB endothelial tight junctions. The permeability of 10 microg x mL(-1) 6-coumarin labeled nanoparticle was 0.29 x 10(-3) cm x min(-1).

CONCLUSIONThis in vitro experimental model of rat BBB was close to resemble the in vivo situation for examination of the permeability of nanoparticle and toxicity evaluation.

Animals ; Animals, Newborn ; Astrocytes ; metabolism ; ultrastructure ; Biological Transport ; Blood-Brain Barrier ; Brain ; blood supply ; cytology ; Capillaries ; cytology ; Cell Membrane Permeability ; Coculture Techniques ; Coumarins ; administration & dosage ; pharmacokinetics ; toxicity ; Endothelial Cells ; metabolism ; ultrastructure ; Factor VIII ; metabolism ; Glial Fibrillary Acidic Protein ; metabolism ; Nanoparticles ; Polyesters ; Polyethylene Glycols ; Rats ; Rats, Sprague-Dawley ; Sucrose ; pharmacokinetics

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

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