Progress of major biomarkers for neonatal brain injury in clinical application / 国际儿科学杂志

With the continuous progress of monitoring and treatment skills, the mortality of neonates has gradually decreased, and the long-term neurodevelopmental outcome has become the primary concern of society and families.During the perinatal period, the developing brain is vulnerable to hypoxia, hemorrhage, infection and inflammation, which may cause varying degrees of brain cell damage.Studies have found that proteins released by damaged brain cells can be detected in the body fluid of neonates, which are related to the occurrence and prognosis of neonatal brain injury.This article mainly reviews the recently reported brain injury biomarkers such as S100B, neuron specific enolase(NSE)and glial fibrillary acidic protein(GFAP)in different biological samples and its clinical predictive value for the occurrence of brain injury and neurodevelopmental prognosis.

Clinical features of autoimmune glial fibrillary acidic protein astrocytopathy in children: an analysis of 34 cases / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features of children with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A).@*METHODS@#A retrospective analysis was performed on the medical data of 34 children with GFAP-A who attended the Department of Neurology, Children's Hospital of Chongqing Medical University, from January 2020 to February 2022. The medical data included clinical manifestations, cerebrospinal fluid features, imaging examination results, treatment, and prognosis.@*RESULTS@#The median age of onset was 8.4 (range 1.9-14.9) years for the 34 children with GFAP-A. The main clinical manifestations included headache (50%, 17/34), fever (47%, 16/34), visual impairment (47%, 16/34), and disturbance of consciousness (44%, 15/34). Abnormal cerebrospinal fluid results were observed in 19 children (56%, 19/34), among whom 8 children had positive autoantibody. The children with overlap syndrome had significantly higher recurrence rate and rate of use of immunosuppressant than those without overlap syndrome (P<0.05). About 77% (24/31) of the children had good response to immunotherapy, and only 1 child had poor prognosis.@*CONCLUSIONS@#Children with GFAP-A often have non-specific clinical symptoms and show good response to immunotherapy. Children with overlap syndrome have a high recurrence rate, and early application of immunosuppressants may help to prevent recurrence and alleviate symptoms.

Effect of Anmeidan on Serum Levels of BDNF， GFAP， and Irisin in Patients with Chronic Insomnia / 中国实验方剂学杂志

ObjectiveTo explore the effect of Anmeidan on the sleep quality and serum levels of brain-derived neurotrophic factor （BDNF）， glial fibrillary acidic protein （GFAP）， and irisin in the patients with chronic insomnia. MethodA multicenter， randomized， double-blind， placebo-controlled clinical study was carried out， including 480 patients with chronic insomnia （deficiency syndrome） in Wuhan （Hubei）， Guangzhou （Guangdong）， and Lanzhou （Gansu）. They were randomized into an observation group and a control group at a ratio of 1∶1. The observation group was orally administered with Anmeidan granules at a dose of 11 g， 3 times per day， and the control group with Anmeidan simulant at a dose of 11 g， 3 times per day， Both groups of patients received sleep education after enrollment. After 4 weeks of medication， the Athens insomnia scale （AIS） scores， Spiegel scale scores， and serum levels of BDNF， GFAP， and irisin were compared between the two groups as well as between before and after treatment. ResultA total of 480 adult patients with chronic insomnia were enrolled in this study， with 64 patients falled off. Finally， the 415 patients were included in the analysis， including 213 patients in the observation group and 202 patients in the control group. There was no difference in age or sex between the two groups of patients. Compared with before treatment， the treatment in both groups decreased the AIS and Spiegel scores （P<0.01）. After treatment， the observation group had lower AIS and Spiegel scores than the control group （P<0.01）. The treatment in the observation group slightly lowered the level of BDNF， elevated the level of irisin （P<0.05）， and lowered the level of GFAP （P<0.05） in the serum. After treatment， the observation group showed higher level of irisin （P<0.05） and lower levels of BDNF and GFAP in the serum than the control group. ConclusionAnmeidan may improve the sleep quality of patients with chronic insomnia by elevating the irisin level and lowering the GFAP level in the serum.

Autoimmune glial fibrillary acidic protein astrocytopathy / 中华神经科杂志

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a rare immune-mediated inflammatory disease of central nervous system reported in recent years, and its specific biological marker is anti-GFAP autoantibody. In this paper, the etiology, pathogenesis, clinical manifestations, auxiliary examination and treatment of the disease are comprehensively expounded, so as to improve the understanding of clinicians, especially neurologists.

Effects of specific knockdown of ribosomal protein S5 in hepatic stellate cells on liver fibrosis / 药学实践杂志

Objective To observe the effect of specific knockdown of hepatic stellate cells (HSC) ribosomal protein S5 (RPS5) on liver fibrosis in rats. Methods The glial fibrillary acidic protein (GFAP) promoter-driven RPS5 shRNA adenovirus was established, and AdGFa2-shRPS5 and its control AdGFa2 shNC were used to transfect primary rat HSCs and hepatocytes, respectively. RPS5 was determined by Western-blot and Real Time PCR, α-SMA and type I collagen expression; the rat liver fibrosis model was established by dimethyl nitrosamine (DMN) and bile duct ligation (BDL), and intrahepatic HSC was specifically knocked down by tail vein injection of adenovirus of RPS5 levels. The pathological changes of liver tissue sections were analyzed by HE staining; the content of hydroxyproline, sections of Sirius red and Masson staining were used to evaluate collagen deposition; immunohistochemical staining was used to detect the expression of α-SMA and RPS5. Results AdGFa2-shRPS5 specifically knocked down the expression level of RPS5 in HSC and increased the expression of α-SMA and type I collagen in vitro. The in vivo results showed that in two animal models of chronic liver injury, specific knockdown of RPS5 expression in HSCs promoted HSC activation, increased the deposition of extracellular matrix, and promoted liver fibrosis. Conclusion RPS5 is essential for HSC activation and liver fibrosis, which could be a potential target for the treatment of liver fibrosis.

Effect of providing purple sweet potato water extract on tumor necrosis factor-α levels, protein 53 expression, glial fibrillary acidic protein expression, brain-derived neurotrophic factor levels, and spatial working memory in rats with d-galactose induction / Efeito do extrato de água de batata doce roxo no fator de necrose tumoral níveis alfa, na expressão da proteína 53, na expressão de proteína ácida fibrilar glial, nos níveis de fator neurotrófico cerebral e na memória espacial em ratos com indução de d-galactose

ABSTRACT. Alzheimer's dementia (AD) is a neurodegenerative disease. The mechanism of oxidative stress in AD is due to amyloid beta (Aβ) protein that aggregates to form plaques, which further triggers chronic inflammation and neuronal apoptosis. Purple sweet potato extract with the main content of anthocyanins is a potential antioxidant with a direct target on the amyloid cascade hypothesis. Objective: The research objective was to determine the role of purple sweet potato water extract as an antioxidant and anti-inflammatory in preventing apoptosis in order to provide a neuroprotective effect in d-galactose-induced rats. Methods: A total of 100 male Wistar rats with randomized posttest-only control group design that met the eligibility criteria were included in this study. The treatment group was given 200 mg/kg BW/day of purple sweet potato water extract on days 1-70. d-galactose induction was administered in the treatment and control groups on days 15-70. Results: The independent t-test showed that the mean tumor necrosis factor-α (TNF-α) levels in the treatment group (735.36±139.74) was significantly lower than that in the control group (896.77±152.52). The p53 and glial fibrillary acidic protein (GFAP) expressions of astrocyte cells in the treatment group were significantly lower than that in the control group. The brain-derived neurotrophic factor (BDNF) levels in the treatment group (498.13±121.47) were higher than that in the control (391.93±140.28), and there was a significant increase in spatial working memory in the treatment group (72.01±10.22) than the control (59.77±11.87). Conclusions: The neuroprotective effect of purple sweet potato extract is due to d-galactose induction resulting from decrease in TNF-α levels, p53 expression, and GFAP expression and increase in BDNF levels and spatial working memory.

RESUMO. A doença de Alzheimer (DA) é uma doença neurodegenerativa. O mecanismo de estresse oxidativo na DA ocorre devido à proteína beta amilóide que se agrega para formar placas que desencadeiam inflamação crônica e apoptose neuronal. O extrato de batata-doce roxa composto principalmente por antocianinas é um potencial antioxidante com efeito direto sobre a hipótese da cascata amilóide. Objetivo: O objetivo da pesquisa foi determinar o papel do extrato aquoso de batata-doce roxa como antioxidante e anti-inflamatório na prevenção da apoptose, para proporcionar um efeito neuroprotetor em ratos induzidos por D-galactose. Métodos: Grupo controle randomizado pós-teste com 100 ratos Wistar machos que preencheram os critérios de elegibilidade. O grupo de tratamento recebeu 200mg/kg de peso corporal/dia de extrato aquoso de batata-doce roxa nos dias 1-70. A indução de D-galactose foi testada nos grupos de tratamento e controle nos dias 15-70. Resultados: O teste t independente mostrou que a média dos níveis de TNF-α no grupo de tratamento (735,36±139,74) foi significativamente menor do que no grupo controle (896,77±152,52). A expressão de p53 e a expressão de GFAP de células de astrócitos foram significativamente menores no grupo de tratamento do que no grupo controle. Os níveis de BDNF no grupo de tratamento (498,13±121,47) foram maiores que no grupo controle (391,93±140,28) e houve um aumento significativo da memória de trabalho espacial no grupo de tratamento (72,01±10,22) em relação ao controle (59,77±11,87). Conclusões: O efeito neuroprotetor do extrato de batata-doce roxa é devido à indução de D-galactose pela diminuição dos níveis de TNF-α, expressão de p53 e expressão de GFAP, aumentando assim os níveis de BDNF e memória espacial.

Effects of excessive fluoride exposure on astrocytes and the expression of glial fibrillary acidic protein in vitro and in vivo / 中华地方病学杂志

Objective:To investigate the effects of excessive fluoride exposure on astrocytes and the expression of glial fibrillary acidic protein (GFAP), in vitro and in vivo. Methods:(1) In vivo experiment: 24 SPF SD rats, half male and half female, were randomly divided into control and fluoride exposed groups according to sex and body weight, 12 rats in each group. Rats were fed with < 1 mg/L and 50 mg/L sodium fluoride solution prepared by tap water for 6 months, respectively. The expression levels of GFAP protein in rat brain tissue were measured by immunofluorescence, immunohistochemistry and Western blotting. (2) In vitro experiment: adult (6-month-old) rat cortical astrocytes were extracted and cultured in primary culture (4 mmol/L sodium fluoride solution for 24 h), and the astrocytes were identified by immunofluorescence, and GFAP mRNA and protein expression levels were detected by real-time fluorescence quantitative PCR and Western blotting, respectively, and astrocytes apoptosis and calcium ion content were detected by flow cytometry. Results:(1) In vivo experiment: the results of immunofluorescence, immunohistochemistry and Western blotting showed that the GFAP protein expression level in brain tissue of rats exposed to fluoride was higher than that of control group (0.440 ± 0.200 vs 0.250 ± 0.120, t =-5.93, P = 0.027; 0.270 ± 0.020 vs 0.240 ± 0.050, t =-4.87, P = 0.040; 1.017 ± 0.001 vs 0.486 ± 0.006, t =-52.48, P = 0.001). (2) In vitro experiment: GFAP positive cells were identified as astrocytes by immunofluorescence; GFAP mRNA expression level was higher in fluoride exposed group than that of control group by real-time fluorescence quantitative PCR (2.780 ± 0.120 vs 0.134 ± 0.005, t =-37.84, P = 0.001). The Western blotting results showed that the GFAP protein expression level was higher in fluoride exposed group than that of control group (2.76 ± 0.10 vs 1.38 ± 0.05, t =-20.44, P = 0.002). Flow cytometry results showed that the apoptosis rate of astrocytes was higher in fluoride exposed group than that of control group (%: 55.0 ± 1.0 vs 3.5 ± 0.6, t =-10.28, P = 0.009) and the calcium ion content was lower than that of control group (%: 54 ± 9 vs 72 ± 13, t = 4.64, P = 0.043). Conclusion:Excessive fluoride exposure causes increased GFAP expression in astrocytes in vitro and in vivo, promotes apoptosis, and affects calcium signaling pathways.

" Multi-hits" based SD rat models of cognitive dysfunction and research on related mechanisms / 中华实用儿科临床杂志

Objective:To establish Sprague-Dawley (SD) rat models of cognitive impairment through repeated stimulation of lipopolysaccharide (LPS) in the early brain development, and to inquire into the effect of " multi-hits" mediated by inflammatory response on the histology and behavior of SD rat models and related molecular mechanisms.Methods:This study adopted a group design for experiments.The " multi-hits" SD rat models were established by intraperitoneal injection of LPS.According to the random number table method, 24 pregnant rats were randomly divided into 4 groups: control group, LPS1 group, LPS2 group and LPS3 group, 6 rats in each group.In the control group, saline was intraperitoneally injected into rats with gestational age of 18 days and 20-day-old neonatal rats.Rats with gestational age of 18 days were intraperitoneally injected with saline in the LPS1 group, 0.05 mg/kg LPS in the LPS2 group, and 0.1 mg/kg LPS in the LPS3 group.The pups in LPS1-3 groups were all injected intraperitoneally with 1 mg/kg LPS at the postnatal age of 20 days.The motor and cognitive function of the pups were evaluated overall by behavioral experiments such as forelimb suspension tests, grid tests and water maze tests.The relative expression of glial fibrillary acidic protein (GFAP), Notch1 and Jagged1 in brain tissue of pups was mainly detected by Western blot (WB) and histological experiments.One-way ANOVA analysis of variance and independent samples t- test were used to compare data among groups and between groups, respectively. Results:(1) Behavioral experiments: compared with the control group, LPS1-3 groups showed progressive decrease in forelimb suspension time [(34.81±5.66) s, (22.47±4.35) s, and (13.20±4.25) s vs.(43.88 ± 4.85) s], and the number of missteps in the grid experiment increased progressively (16.13±2.90, 20.75±3.10, 25.13±4.45 vs.9.00±2.72). The differences were statistically significant ( F=69.77, 35.59, all P<0.001). Both the escape latency and total distance in Morri′s water maze test increased progressively ( P<0.05). (2) WB experiment: the relative expression levels of GFAP, Notch1 and Jagged1 proteins in LPS1-3 groups were significantly higher than that in the control group ( P<0.05). (3) Hematoxylin-eosin (HE) staining and electron microscope pathology: compared with the control group, LPS1-3 groups had more loosely arranged frontal cortices and more obvious cell pyknosis.Under the electron microscope, the cytoplasm was swelling to varying degrees, mitochondrial cristae were broken, and part of the nuclear membrane was damaged. Conclusions:In the " multi-hits" cognitive impairment model, the damage to the brain tissue structure and behavioral changes of pups may be related to the up-regulation of Notch1/Jagged1 pathway mediated by repeated exposure to LPS.

Effect of vagus nerve stimulation by electroacupuncture on GFAP and NeuN in hippocampal of juvenile rats with depression induced by chronic unpredictable stress / 中国医师杂志

Objective:To analyze the expression of glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) antigen in hippocampus based on the depression model of juvenile rats caused by chronic unpredictable stress (CUS), and to explore the effect of electroacupuncture vagus nerve on CUS depression model.Methods:Six juvenile SD rats were selected as the control group (without any stimulation), and the rest were divided into CUS group, pseudo stimulation group, fluoxetine group and electroacupuncture group by random number method after CUS modeling, with 6 rats in each group. Fluoxetine group was given 10 mg/kg fluoxetine intervention; control group and CUS group were given the same amount of normal saline intervention; In the electroacupuncture group, the distal vagus nerve was stimulated after ligation, while in the pseudo stimulation group, only vagus nerve was isolated without electrical stimulation. After 28 d of intervention, the five groups were subjected to Open-field Test and Sucrose Preference Test. Hippocampal neurons were detected by hematoxylin and eosin (HE) staining, and the expressions of GFAP and NeuN in hippocampal were detected by immunohistochemistry.Results:After CUS modeling and before intervention, the number of vertical and horizontal movements, sucrose consumption and sucrose preference in CUS group, pseudo stimulation group, fluoxetine group and electroacupuncture group were significantly lower than those in the control group (all P<0.01); After the intervention, the above indexes in CUS group and pseudo stimulation group were still lower than those in the control group (all P<0.01), but the above indexes in fluoxetine group and electroacupuncture group were significantly higher than those in CUS group and pseudo stimulation group (all P<0.01). HE staining showed that the arrangement of hippocampal neurons in CUS group and pseudo stimulation group were loose, and there were cell swelling and pyknosis, which was significantly improved in fluoxetine group and electroacupuncture group. Immunohistochemical results showed that compared with the control group, the expression of GFAP increased and NeuN decreased in the hippocampus of CUS group and pseudo stimulation group (all P<0.01); Compared with CUS group and pseudo stimulation group, the expression of GFAP decreased and NeuN increased in fluoxetine group and electroacupuncture group (all P<0.01). Conclusions:Electroacupuncture of vagus nerve can obviously improve the depression symptoms of juvenile rats, which is similar to fluoxetine, and may be related to regulating the expression of GFAP and Neun in hippocampus.

Clinical significance of prognostic serum marker expression in older adult patients with sepsis-associated encephalopathy / 中国基层医药

Objective:To investigate the clinical significance of prognostic serum marker expression in older adult patients with sepsis-associated encephalopathy (SAE).Methods:The clinical data of 79 older adult patients with SAE who received treatment in The Second People's Hospital of Hefei from June 2019 to February 2021 (study group) and 121 sepsis patients without encephalopathy concurrently (control group) were retrospectively analyzed. The indexes with statistically significant difference between the two groups were subjected to multivariate binary logistic regression. Survival curve was plotted.Results:There were no significant differences in neuron specific enolase [NSE, (10.69 ± 4.31) μg/L vs. (24.84 ± 3.28) μg/L, t = 26.25, P < 0.01], S100β [(0.25 ± 0.06) μg/L vs. (0.53 ± 0.09) μg/L, t = 22.45, P < 0.01], monocyte chemoattractant protein-1 [MCP-1, (99.33 ± 4.87) ng/L vs. (179.99 ± 6.02) ng/L, t = 99.94, P < 0.01], malondialdehyde [MDA, (4.22 ± 0.08) nmol/L vs. (6.78 ± 0.11) nmol/L, t = 33.76, P < 0.01], glial fibrillary acidic protein [GFAP, (0.21±0.08) μg/L vs. (2.03 ± 0.47) μg/L, t = 33.76, P < 0.01], procalcitonin [(7.04 ± 2.50) ng/L vs. (16.23 ± 2.48) ng/L, t = 25.47, P < 0.01], interleukin-6 [(29.91 ± 4.51) ng/L vs. (69.22 ± 6.79) ng/L, t = 45.51, P < 0.01], Acute Physiology and Chronic Health Evaluation II (APACHE II) score [(18.33 ± 2.12) points vs. (28.89 ± 5.09) points, t = 17.53, P < 0.01], and sequential organ failure assessment score [(7.69 ± 1.50) points vs. (14.05 ± 1.55) points, t = 28.92, P < 0.01] between the control and study groups. N-terminal pro B-type natriuretic peptide was (868.38 ± 25.28) ng/L and (1 037.19 ± 25.34) ng/L in the control and study groups, respectively. Logistic regression analysis revealed that NSE, MCP-1, MDA, and GFAP were the independent risk factors for developing SAE in older adults (NSE: t = 8.42, P < 0.01; MCP-1: t = 4.16, P < 0.01; MDA: t = 18.4, P < 0.01; GFAP: t = 2.88, P < 0.01). The survival curve indicated that survival rate was significantly lower in the study group than in the control group. Conclusion:NSE, MCP-1, MDA, and GFAP are independent risk factors for developing SAE in older adults.

Protective Effects of Anmeidan on Cell Structure Against Neuronal Damage in Hippocampal CA1 Region of Sleep-deprived Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Anmeidan （AMD） on neuronal structure and neuronal marker protein expression in the hippocampal CA1 region of sleep-deprived （SD） rats. MethodRats were randomly divided into control group， model group， an AMD group （9.09 g·kg-1·d-1）， and melatonin group （0.27 g·kg-1·d-1）. Rats in the control group and the model group received equal volumes of physiologicol saline. The SD model was induced by the self-made sleep deprivation box for four weeks. Ethovision XT system detected and analyzed the spontaneous behaviors of rats. The histomorphology of neurons in the hippocampal CA1 region was observed by hematoxylin-eosin （HE） staining and Nissl staining， and the changes in Nissl bodies were observed by Nissl staining. The ultrastructure of hippocampal cells was observed by transmission electron microscopy （TEM）. Immunohistochemistry was used to detect the expression of glial fibrillary acidic protein （GFAP）， microtubule-associated protein 2 （MAP2）， nestin， and neuronal nuclei （NeuN） in the CA1 region. ResultCompared with the control group， the model group showed longer distance， increased average activity speed， cumulative duration， average body fill， and higher activity frequency （P<0.01）. Besides， the neurons in the CA1 region were reduced in number with disorganized arrangement， wrinkled nuclei， deeply stained cytoplasm， reduced Nissl bodies， swollen and deformed mitochondria， shortened cristae， and swollen Golgi vesicles. Furthermore， the mean integral absorbance （IA） value of GFAP increased and those of MAP2， nestin， and NeuN decreased （P<0.01）. Compared with the model group， the AMD group showed shortened distance traveled， lower average activity speed， shorter cumulative duration， decreased average body fill， and reduced activity frequency （P<0.05， P<0.01）. Moreover， the neurons in the CA1 region were relieved from damage with increased cell number， clear nuclei and cytoplasm， increased Nissl bodies， and relieved mitochondrial damage. The IA value of GFAP decreased and those of MAP2， nestin， and NeuN increased （P<0.05， P<0.01）. ConclusionAMD can improve structural damage of neurons in the hippocampal CA1 region of sleep-deprived rats， which may be achieved by decreasing GFAP expression and increasing MAP2， nestin， and NeuN expression.

Clinical Features of Multicenter Autoimmune Glial Fibrillary Acidic Protein Astrocytosis / 罕见病研究

  Objective  To investigate the clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.  Methods  We collected and analyzed the clinical and laboratory data and obtained the clinical characteristics of diagnosis and treatment from fifteen patients with positive GFAP antibody tested by cerebrospinal fluid and diagnosed autoimmune GFAP astrocytopathy by the multi-centers.  Results  The mean age of the first onset of autoimmune GFAP astrocytopathy was 39.73 years old (range 4-65 years), with no significant gender difference. In terms of clinical manifestations, we found the whole brain symptoms including abnormal mental behavior, disturbance of consciousness, epileptic attack accounting for more than 50, , meningitis accounting for 66.7%, myelitis (53.3%), limb tremor (53.3%), vision loss (33.3%); systemic symptoms including fever(100%) and fatigue(86.7%). 46.7% of patients were initially diagnosed with tuberculous meningoencephalitis and were treated with diagnostic antituberculous therapy. The MRI showed 46.7% of patients showed brain linear perivascular radial gadolinium enhancement in the white matter perpendicular to the ventricle.  Conclusions  Autoimmune GFAP astrocytopathy are acute or subacute dieases and the main clinical features include encephalitis, meningitis, myelitis and optic neuritis. They are likely to be misdiagnosed as tuberculous meningoencephalitis and can manifest progressive loss of consciousness in early phase, which is even life threatening.

Clinical significance of serum glial fibrillary acidic protein level in middle-aged and elderly patients with Parkinson's disease / 中华老年医学杂志

Objective:To investigate the clinical significance of serum glial fibrillary acidic protein(GFAP)level in middle-aged and elderly patients with Parkinson's disease(PD).Methods:In the prospective study, a total of 39 patients with PD hospitalized in the Department of Neurology of Zhejiang Hospital affiliated to Zhejiang University School of Medicine, and 17 healthy subjects from January 2017 to May 2021 were collected.Serum GFAP levels in the PD group and healthy control(CT)group were detected by an ultra-sensitive Simoa hypersensitive protein detection technology.The correlations of serum GFAP level with age, gender, clinical presentation type, depression score, Montreal Cognitive Assessment Scale(MOCA)score and Mini-Mental State Examination(MMSE)score were analyzed.Results:The level of serum GFAP was significantly higher in PD group(219.6±166.2)ng/L than in CT group(109.9±56.6)ng/L( P< 0.01). In PD group, there was no correlation of serum GFAP with age, gender, clinical classification, depression and MOCA score(age: r=0.042, gender: r=-0.142, depression score: r=0.076, MoCA score: r=0.014, all P>0.05); but there was a significant negative correlation between serum GFAP and MMSE score( r=-0.433, P< 0.05). Conclusions:There is a negative correlation between serum GFAP level and MMSE score, suggesting that the increase of serum GFAP might be suggestive of cognitive decline in Parkinson's disease patients to some extent, which should be paid attention to in clinical work.

Autoimmune glial fibrillary acidic protein astrocytopathy / 中国小儿急救医学

Autoimmune glial fibrillary acidic protein astrocytopathy(GFAP-A) is a novel form of autoimmune meningo-encephalitis resulted from auto-antibodies to GFAP, which may involve meninges, brain, spinal cord and optic nerves.Clinical presentations and outcomes in children are similar with those in adults.Compared with adults with GFAP-A, autonomic dysfunction, brain stem dysfunction or co-existing NMDAR encephalitis are more frequently in children, whereas malignancy and relapse are more commonly seen in the adults.GFAP-IgG level detected in cerebrospinal fluid is a specific biomarker of autoimmune GFAP-A.Corticosteroid-responsiveness is also a hallmark of autoimmune GFAP-A.

The effect of rosmarinic acid on deformities occurring in brain tissue by craniectomy method. Histopathological evaluation of IBA-1 and GFAP expressions

Abstract Purpose To investigate the role of Rosmarinic acid (RA) in the prevention of traumatic brain injury and the immunohistochemical analysis of IBA-1 and GFAP expressions. Methods Healthy male rats were randomly divided into 3 groups consisting of 10 rats. Groups were as follows; control group, traumatic brain injury (TBI) group, and TBI+RA group. After traumatic brain injury, blood samples were taken from the animals and analyzed with various biochemical markers. And then IBA-1 and GFAP expressions were evaluated immunohistochemically. Results Significant results were obtained in all biochemical parameters between groups. Immunohistochemical sections showed IBA-1 not only in microglia and macrophage activity but also in degenerative neurons in blood vessel endothelial cells. However, GFAP reaction and post-traumatic rosmarinic acid administration showed positive expression in astrocytes with regular structure around the blood vessel. Conclusion Rosmarinic acid in blood vessel endothelial cells showed that preserving the integrity of astrocytic structure in the blood brain barrier may be an important antioxidant.

Silencing GFAP gene regulates the proliferation and apoptosis of high glucose-induced retinal microvascular endothelial cells / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To investigate the effect of silencing glial fibrillary acidic protein gene(GFAP)on proliferation and apoptosis of high glucose-induced human retinal microvascular endothelial cells(hRMECs)and its mechanism.<p>METHODS: Expression of GFAP in hRMECs treated with high sugar(30mmol/mL)and low sugar(5mmol/mL)was detected by qRT-PCR. The high glucose-induced hRMECs cells of silencing GFAP gene was established by lentiviral-mediated method. High glucose-induced hRMECs cells were treated with SRI-011381(TGF-β signaling pathway activator)and dimethyl sulfoxide(DMSO); Expression of GFAP, transforming growth factor-1(TGF-β1), activating transcription factor2(Smad2), Smad3 proteins were measured by Western blot, and cell proliferation and apoptosis were detected by CCK-8 and flow cytometry, respectively.<p>RESULTS: Expression of GFAP was significantly increased in high glucose treated hRMECs. The high glucose induced hRMECs cell model of GFAP gene silencing was successfully constructed by lentivirus mediation, and the cell proliferation ability was significantly improved, the apoptosis rate is significantly inhibited, and expression of TGF-1, Smad2 and Smad3 proteins in the TGF-β signaling pathway was significantly inhibited after silencing GFAP, while activation of TGF-β signaling pathway could reverse the inhibitory effect of silencing GFAP on the proliferation and apoptosis in high glucose hRMECs.<p>CONCLUSION: Silencing GFAP gene can promote the proliferation of high glucoseinducedhuman retinal microvascular endothelial cells and inhibit cell apoptosis,the mechanism may be related to the inactivation of TGF-β signaling pathway.

In vitro differentiation potential of human urine-derived stem cells into neuron-like cells and their protective effects against spinal cord injury in rats / 中国组织工程研究

BACKGROUND: Human urine-derived stem cells are newly discovered adult stem cells, characterized by rich sources, simple extraction, good proliferative ability and multi-directional differentiation potential. In recent years, human urine-derived stem cells have been used for the repair of neurological functions in urinary diseases, such as stress urinary incontinence and vesicoureteral reflux. OBJECTIVE: To explore the biological characteristics of human urine-derived stem cells and to study their repairing effect in a rat model of spinal cord injury. METHODS: Cell phenotypes of human urine-derived stem cells were detected using flow cytometry, and the immunohistochemical staining was used to identify neuron-like cells differentiated from human urine-derived mesenchymal stem cells. Then, an animal model of spinal cord injury at T9 segment was made by Allen method, and after modeling 24 Sprague-Dawley rats were assigned into spinal cord injury group or cell treatment group (n=12/group). In the cell treatment group, the model rats were injected 2 μL of 1.0×1011/L human urine-derived stem cells, while in the spinal cord injury group, the rats were administered the same volume of L-DMEM containing 10% fetal bovine serum. Basso, Beattie and Bresnahan scores were valued at 1, 10, 20, and 30 days after modeling. Spinal cord samples from all the rats were taken out at 30 days after modeling, and Luxol Fast Blue staining, microglia/macrophages staining and glial fibrillary acidic protein staining were used to value the injured area of the spinal cord and the fluorescence intensity of glial fibrillary acidic protein. RESULTS AND CONCLUSION: (1) Flow cytometry showed high expression on CD29 and CD90, and low expression on CD45 in human urine-derived mesenchymal stem cells. Moreover, human urine-derived mesenchymal stem cells could be induced to differentiating into neuron-like cells in vitro. (2) Basso, Beattie and Bresnahan scores showed no significant difference between the two groups at 1 and 10 days after modeling (P > 0.05), while, at 20 and 30 days after modeling, the scores in the cell treatment group were significantly higher than those in the spinal cord injury group (P < 0.05). (3) Luxol Fast Blue staining showed that the injured area of the spinal cord in the cell treatment group was markedly less than that in the spinal cord injury group (P < 0.05), and the glial fibrillary acidic protein showed lower fluorescence intensity in the cell treatment group than the spinal cord injury group (P < 0.05). To conclude, human urine-derived stem cells can differentiate into neuron-like cells and have therapeutic effects in the rat model of spinal cord injury.

Effects of bone marrow mononuclear cell transplantation on the recovery of nerve function after focal cerebral ischemia and reperfusion / 中华物理医学与康复杂志

Objective@#To determine the effect of transplanting bone marrow mononuclear cells (BMMCs) on the expression of glial fibrillary acidic protein (GFAP) and Nogo-A around the ischemic foci after focal cerebral ischemia and reperfusion, and to study any role of BMMCs in nerve function recovery.@*Methods@#BMMCs were isolated from the bone marrow of Sprague-Dawley rats. Cerebral ischemia and reperfusion was performed using a nylon thread to occlude the right middle cerebral artery for 2h followed by 24h of reperfusion. The qualified models were selected according to the Longa scale. The 48 models selected were randomly divided into a model group and an observation group, each of 24. Each group was further divided into 7d, 14d and 21d subgroups. 100μl of BMMCs (5×106 /ml) were slowly injected into the ischemic lateral striata of the observation group. The rats in the model group were similarly injected, but with buffered saline solution. The rats were evaluated using the Longa scale after 7d, 14d and 21d. The rats were then sacrificed and the brain was resected. Immunohistochemical assays quantified the expression of GFAP and Nogo-A around the ischemic foci.@*Results@#Compared with the model group, the rats in the observation group showed less neurological deficit on the 21st day, significantly greater expression of GFAP and significantly less Nogo-A expression on days 14 and 21. Nogo-A expression on the 21st day was also significantly lower than on the 14th day in the observation group.@*Conclusion@#BMMC transplantation can promote recovery from nerve damage after focal cerebral ischemia, which is probably related to enhanced expression of GFAP and restrained expression of Nogo-A in the brain tissues surrounding ischemic lesions.

Effect of aquaporin 4 gene knockout on neuropathic pain and its possible mechanism / 国际药学研究杂志

Objective: To investigate the effect of aquaporin 4(AQP4)in neuropathic pain and explore the rela- tionship with the activation of spinal astrocytes and release of proinflammatory cytokines. Methods: The effect of AQP4 gene knockout(KO)on the pain-related behavior was investigated using the sciatic nerve branch injury model(SNI)of AQP4 KO and wild type(WT)mice. The expression of astrocyte activation-related protein,glial fibrillary acidic protein(GFAP),and the level of proinflammatory cytokines,TNF-α and IL-6,all in the mouse spinal cord samples,were detect- ed by Western blot(WB)and ELISA,respectively. Results: After SNI surgery,compared with the WT group,a signifi- cant attenuation in mechanical allodynia was found in the KO group(P<0.01),however,no difference was detected be- tween two sham groups(Sham)of WT and KO mice(P>0.05). These results indicated that the AQP4 gene knockout re- lieved neuropathic pain. Fouteen days after SNI surgery,WB results showed that the GFAP level in mouse spinal cord was significantly higher in the WT-SNI group than in the WT-Sham group(P<0.01),whereas the GFAP level in the KOSNI group was significantly lower than that in the WT-SNI group(P<0.01). These results indicated that AQP4 KO inhib- ited activation of spinal astrocytes in SNI model mice. In addition,14 days after SNI surgery,ELISA results showed that the levels of mouse spinal cord proinflammatory cytokines,TNF-α and IL-6 in the WT-SNI group were significantly high- er than those in the WT-Sham group(P<0.05 and P<0.01,respectively),whereas the levels of TNF-α and IL-6 in the KO-SNI group were significantly lower than those in the WT-SNI group(P<0.05 and P<0.01,respectively). These re- sults indicated that AQP4 KO inhibited the level of mouse spinal cord proinflammatory cytokines in SNI model mice. Conclusion: The AQP4 gene knockout may relieve the neuropathic pain via the inhibition of the astrocyte activation and proinflammatory cytokine release.

Relationship between microangiogenesis and astrocytes after cerebral infarct in SHR-SP rats / 西安交通大学学报(医学版)

Objective: To investigate the possible role of astrocytes after brain infarction in stroke-prone, spontaneously hypertensive (SHR-SP) rats and the association with angiogenesis and the architecture. Methods: We maintained SHR-SP rats on high sodium water starting to accelerate the stroke onset. The 3D quantification of microvasculatures (diameter, branch number) by cofocal microscope after FITC-dextran was injected into the rats via the left femoral vein. Glial fibrillary acidic protein (GFAP) expression and microvessel density (MVD) using counting the number of factor -positive endothelial cells were evaluated by immunofluorescence and immunohistochemistry, respectively. Results: Cerebral infarction occurred at week 7 after high sodium water intake (13 g/L NaCl) in SHR-SP group. When compared with the non-infarcted contralateral hemisphere and SHR-SP on normal sodium intake and WKY rats, GFAP expression and MVD were significantly increased, respectively, and the diameter and the branch number of vessels were decreased, respectively, in cerebral infarcts with boundary zones of SHR-SP rats (P<0.01). Linear correlation analysis showed that GFAP expression was positively correlated with MVD and the diameter and the branch number of vessels in cerebral infarcts in SHR-SP (P<0.01). Conclusion: Astrocytes hyperplasia may be associated with increased regional angiogenesis and the changes of architecture in SHR-SP rats with high sodium water (13 g/L NaCl) that induces focal cerebral infarcts.