BACKGROUND Brain gliomas are malignant tumors with high postoperative recurrence rates.Early prediction of prognosis using specific indicators is of great significance.AIM To assess changes in ubiquitin carboxy-termin...BACKGROUND Brain gliomas are malignant tumors with high postoperative recurrence rates.Early prediction of prognosis using specific indicators is of great significance.AIM To assess changes in ubiquitin carboxy-terminal hydrolase L1(UCH-L1)and glial fibrillary acidic protein(GFAP)levels in patients with glioma pre-and postoperatively.METHODS Between June 2018 and June 2021,91 patients with gliomas who underwent surgery at our hospital were enrolled in the glioma group.Sixty healthy volunteers were included in the control group.Serum UCH-L1 and GFAP levels were measured in peripheral blood collected from patients with glioma before and 3 d after surgery.UCH-L1 and GFAP levels in patients with glioma with different clinicopathological characteristics were compared before and after surgery.The patients were followed-up until February 2022.Postoperative glioma recurrence was recorded to determine the serum UCH-L1 and GFAP levels,which could assist in predicting postoperative glioma recurrence.RESULTS UCH-L1 and GFAP levels in patients with glioma decreased significantly 3 d after surgery compared to those before therapy(P<0.05).However,UCH-L1 and GFAP levels in the glioma group were significantly higher than those in the control group before and after surgery(P<0.05).There were no statistically significant differences in preoperative serum UCH-L1 and GFAP levels among patients with glioma according to sex,age,pathological type,tumor location,or number of lesions(P>0.05).Serum UCH-L1 and GFAP levels were significantly lower in the patients with WHO grade I-II tumors than in those with gradeⅢ-IV tumors(P<0.05).Serum UCH-L1 and GFAP levels were lower in the patients with tumor diameter≤5 cm than in those with diameter>5 cm,in which the differences were statistically significant(P<0.05).Glioma recurred in 22 patients.The preoperative and 3-d postoperative serum UCH-L1 and GFAP levels were significantly higher in the recurrence group than these in the non-recurrence group(P<0.05).Receiver operating characteristic curves were plotted.The areas under the curves of preoperative serum UCH-L1 and GFAP levels for predicting postoperative glioma recurrence were 0.785 and 0.775,respectively.However,the efficacy of serum UCH-L1 and GFAP levels 3 d after surgery in predicting postoperative glioma recurrence was slightly lower compared with their preoperative levels.CONCLUSION UCH-L1 and GFAP efficiently reflected the development and recurrence of gliomas and could be used as potential indicators for the recurrence and prognosis of glioma.展开更多
Objective The present study aimed to explore the role of P2Y1 receptor in glial fibrillary acidic protein （GFAP） production and glial cell line-derived neurotrophic factor （GDNF） secretion of astrocytes under isch...Objective The present study aimed to explore the role of P2Y1 receptor in glial fibrillary acidic protein （GFAP） production and glial cell line-derived neurotrophic factor （GDNF） secretion of astrocytes under ischemic insult and the related signaling pathways. Methods Using transient right middle cerebral artery occlusion （tMCAO） and oxygen-glucose-serum deprivation for 2 h as the model of ischemic injury in vivo and in vitro, immunofluorescence, quantitative real-time reverse transcription-polymerase chain reaction （RT-PCR）, Western blotting, enzyme linked immunosorbent assay （ELISA） were used to investigate location of P2Y1 receptor and GDNF, the expression of GFAP and GDNF, and the changes of signaling molecules. Results Blockage of P2Y1 receptor with the selective antagonist N^6-methyl-2′-deoxyadenosine 3′,5′-bisphosphate diammonium （MRS2179） reduced GFAP production and increased GDNF production in the antagonist group as compared with simple ischemic group both in vivo and in vitro. Oxygen-glucose-serum deprivation and blockage of P2Y1 receptor caused elevation of phosphorylated Akt and cAMP response element binding protein （CREB）, and reduction of phosphorylated Janus kinase2 （JAK2） and signal transducer and activator of transcription3 （STAT3, Ser727）. After blockage of P2Y1 receptor and deprivation of oxygen-glucose-serum, AG490 （inhibitor of JAK2） reduced phosphorylation of STAT3 （Ser727） as well as expression of GFAP; LY294002, an inhibitor of phosphatidylinositol 3-kinase （PI3-K）, decreased phosphorylation of Akt and CREB; the inhibitor of mitogen-activated protein kinase kinase 1/2 （MEK 1/2） U0126, an important molecule of Ras/extracellular signal- regulated kinase （ERK） signaling pathway, decreased the phosphorylation of JAK2, STAT3 （Ser727）, Akt and CREB. Conclusion These results suggest that P2Y1 receptor plays a role in the production of GFAP and GDNF in astrocytes under transient ischemic condition and the related signaling pathways may be JAK2/STAT3 and PI3-K/Akt/CREB, respectively, and that crosstalk probably exists between them.展开更多
Electroacupuncture(EA)has been shown to reduce blood lipid level and improve cerebral ischemia in rats with hyperlipemia complicated by cerebral ischemia.However,there are few studies on the results and mechanism of t...Electroacupuncture(EA)has been shown to reduce blood lipid level and improve cerebral ischemia in rats with hyperlipemia complicated by cerebral ischemia.However,there are few studies on the results and mechanism of the effect of EA in reducing blood lipid level or promoting neural repair after stroke in hyperlipidemic subjects.In this study,EA was applied to a rat model of hyperlipidemia and middle cerebral artery thrombosis and the condition of neurons and astrocytes after hippocampal injury was assessed.Except for the normal group,rats in other groups were fed a high-fat diet throughout the whole experiment.Hyperlipidemia models were established in rats fed a high-fat diet for 6 weeks.Middle cerebral artery thrombus models were induced by pasting 50%FeCl3 filter paper on the left middle cerebral artery for 20 minutes on day 50 as the model group.EA1 group rats received EA at bilateral ST40(Fenglong)for 7 days before the thrombosis.Rats in the EA1 and EA2 groups received EA at GV20(Baihui)and bilateral ST40 for 14 days after model establishment.Neuronal health was assessed by hematoxylin-eosin staining in the brain.Hyperlipidemia was assessed by biochemical methods that measured total cholesterol,triglyceride,low-density lipoprotein and high-density lipoprotein in blood sera.Behavioral analysis was used to confirm the establishment of the model.Immunohistochemical methods were used to detect the expression of glial fibrillary acidic protein and nerve growth factor in the hippocampal CA1 region.The results demonstrated that,compared with the model group,blood lipid levels significantly decreased,glial fibrillary acidic protein immunoreactivity was significantly weakened and nerve growth factor immunoreactivity was significantly enhanced in the EA1 and EA2 groups.The repair effect was superior in the EA1 group than in the EA2 group.These findings confirm that EA can reduce blood lipid,inhibit glial fibrillary acidic protein expression and promote nerve growth factor expression in the hippocampal CA1 region after hyperlipidemia and middle cerebral artery thrombosis.All experimental procedures and protocols were approved by the Animal Use and Management Committee of Beijing University of Chinese Medicine,China(approval No.BUCM-3-2018022802-1002)on April 12,2018.展开更多
AIM：To assess the expression of nestin and glial fibrillary acidic protein（GFAP）in rat retina after optic nerve transection.METHODS：Rats were randomly divided into normal control group,sham group and operation gro...AIM：To assess the expression of nestin and glial fibrillary acidic protein（GFAP）in rat retina after optic nerve transection.METHODS：Rats were randomly divided into normal control group,sham group and operation group,and used for establishing an animal model of optic nerve transection.Retinal specimen of each group was collected at 3,48h,7and 14d postoperative.Nestin and GFAP expressions on sagittal sections were analyzed by immunohistochemical staining,and protein extraction was analyzed by Western blot.RESULTS：Immunohistochemical analysis showed that nestin positive staining was rarely detected in normal control group and sham group,while sham group showed weak positive staining at 3h postoperative,the reaction gradually increased at 48h postoperative,and reached its maximum at 7d postoperative,and then decreased at 14d postoperative.Compared to the expression of GFAP,there was not statistically significant obvious difference among three groups（P〉0.05）.Result of Western blot method was consistent with that of immunohistochemical method.CONCLUSION：The expression of nestin increased in a time dependent fashion in Müller cells of retina following optic nerve transection,which was statistically significant,but there was no obvious difference in GFAP expression.The results indicate that an increase in colloid synthesis in retina following optic nerve transection can improve the retinal neurons’environment.展开更多
Emerging evidence has suggested global histone H4 acetylation status plays an important role in neural plasticity. For instance, the imbalance of this epigenetic marker has been hypothesized as a key factor for the de...Emerging evidence has suggested global histone H4 acetylation status plays an important role in neural plasticity. For instance, the imbalance of this epigenetic marker has been hypothesized as a key factor for the development and progression of several neurological diseases. Likewise, astrocytic reactivity-a wellknown process that markedly influences the tissue remodeling after a central nervous system injury-is crucial for tissue remodeling after spinal cord injury（SCI）. However, the linkage between the above-mentioned mechanisms after SCI remains poorly understood. We sought to investigate the relation between both glial fibrillary acidic protein（GFAP） and S100 calcium-binding protein B（S100B）（astrocytic reactivity classical markers） and global histone H4 acetylation levels. Sixty-one male Wistar rats（aged ~3 months） were divided into the following groups： sham; 6 hours post-SCI; 24 hours post-SCI; 48 hours post-SCI; 72 hours post-SCI; and 7 days post-SCI. The results suggested that GFAP, but not S100B was associated with global histone H4 acetylation levels. Moreover, global histone H4 acetylation levels exhibited a complex pattern after SCI, encompassing at least three clearly defined phases（first phase： no changes in the 6, 24 and 48 hours post-SCI groups; second phase： increased levels in the 72 hours post-SCI group; and a third phase： return to levels similar to control in the 7 days post-SCI group）. Overall, these findings suggest global H4 acetylation levels exhibit distinct patterns of expression during the first week post-SCI, which may be associated with GFAP levels in the perilesional tissue. Current data encourage studies using H4 acetylation as a possible biomarker for tissue remodeling after spinal cord injury.展开更多
The present study analyzed the effects of ethanol extracts of scorpion on epilepsy prevention and hippocampal expression of glial fibrillary acidic protein in a lithium chloride-pilocarpine epileptic rat model. Result...The present study analyzed the effects of ethanol extracts of scorpion on epilepsy prevention and hippocampal expression of glial fibrillary acidic protein in a lithium chloride-pilocarpine epileptic rat model. Results were subsequently compared with valproic acid. Results showed gradually- increased hippocampal glial fibrillary acidic protein expression following model establishment; glial fibrillary acidic protein mRNA expression was significantly increased at 3 days, reached a peak at 7 days, and then gradually decreased thereafter. Ethanol extracts of scorpion doses of 580 and 1 160 mg/kg, as well as 120 mg/kg valproic acid, led to a decreased number of glial fibrillary acidic protein-positive cells and glial fibrillary acidic protein mRNA expression, as well as decreased seizure grades and frequency of spontaneously recurrent seizures. The effects of 1 160 mg/kg ethanol extracts of scorpion were equal to those of 120 mg/kg valproic acid. These results suggested that the anti-epileptic effect of ethanol extracts of scorpion were associated with decreased hippocampal glial fibrillary acidic protein expression in a rat model of lithium chlofide-pilocarpine induced epilepsy.展开更多
BACKGROUND： Gamma-aminobutyric acid transporter plays an important role in gamma-aminobutyric acid metabolism, and is highly associated with epilepsy seizures. Pathologically, astrocytes release active substances tha...BACKGROUND： Gamma-aminobutyric acid transporter plays an important role in gamma-aminobutyric acid metabolism, and is highly associated with epilepsy seizures. Pathologically, astrocytes release active substances that alter neuronal excitability, and it has been demonstrated that astrocytes play a role in epileptic seizures. OBJECTIVE： To observe changes in gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression in the hippocampus and cortex of the temporal lobe in rats with pentylenetetrazol-induced chronic epilepsy. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment was performed at the Department of Neurobiology, Third Military University of Chinese PLA between January 2006 and December 2007. MATERIALS： Pentylenetetrazol was purchased from Sigma, USA; rabbit anti-rat gammaaminobutyric acid transporter 1 and glial fibrillary acidic protein were from Chemicon, USA. METHODS： A total of 40 Sprague Dawley rats were divided into model and control groups. Rat models of chronic epilepsy were created by pentylenetetrazol kindling, and were subdivided into 3-, 7-, and 14-day kindling subgroups. MAIN OUTCOME MEASURES： Gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression, as well as the number of positive cells in the hippocampus and cortex of temporal lobe of rats, were determined by immunohistochemistry and Western blot analyses. RESULTS： Compared with the control group, the number of gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein -positive cells in the hippocampus and cortex of rats with pentylenetetrazol-induced epilepsy significantly increased, gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression increased after 3 days of kindling, reached a peak on day 7, and remained at elevated levels at day 14 （P〈 0.05）. CONCLUSION： Astrocytic activation and gamma-aminobutyric acid transporter 1 overexpression may contribute to pentylenetetrazol-induced epilepsy.展开更多
Diverse neurotoxic insults result in proliferation and hypertrophy of astrocytes. The hallmark of this response is enhanced expression of the major intermediate filament protein of astrocytes, glial fibrillary acidic ...Diverse neurotoxic insults result in proliferation and hypertrophy of astrocytes. The hallmark of this response is enhanced expression of the major intermediate filament protein of astrocytes, glial fibrillary acidic protein (GFAP). These observations suggest that GFAP may be a useful biomarker of neurotoxicity. To investigate this possibility, we administered prototype neurotoxicants to experimental animals and assessed the effects of these agents on the tissue content of GFAP, as determined by radioimmunoassay. A review of the background, design, and results of these experiments are presented in this paper. Our findings indicate that GFAP is a sensitive and specific biomarker of neurotoxicity.展开更多
Astrocytes can alter their appearance and become reactive following chronic cerebral ischemia. In the present study, a rat model of chronic cerebral ischemia was treated with 50 and 100 mg/kg curcumin. Results showed ...Astrocytes can alter their appearance and become reactive following chronic cerebral ischemia. In the present study, a rat model of chronic cerebral ischemia was treated with 50 and 100 mg/kg curcumin. Results showed that pathological changes of neuronal injury in hippocampal CA1 area of rats induced by chronic cerebral ischemia were attenuated, as well as upregulated expression of glial fibriliary acidic protein and nestin, in a dose-dependent manner.展开更多
Vascular dementia produced by permanent ligation of bilateral common carotid arteries involves progressive deterioration of intellectual and cognitive function in rats, which are closely associated with the hippocampu...Vascular dementia produced by permanent ligation of bilateral common carotid arteries involves progressive deterioration of intellectual and cognitive function in rats, which are closely associated with the hippocampus. This study used immunohistochemical analysis to detect the expression of glial fibrillary acidic protein and nestin in the hippocampus in a vascular dementia model. The results revealed that both glial fibrillary acidic protein and nestin expression were increased 1 day after permanent ligation of the bilateral common carotid arteries, compared with a sham-operated group. The expression of glial fibrillary acidic protein peaked at 7 days post-surgery. The expression of nestin was a little weaker than that of glial fibrillary acidic protein, and peaked at 14 days （P 〈 0.01）. The expression of both proteins slightly decreased at 21 and 28 days, accompanied by recovery of cerebral blood flow. In conclusion, this study demonstrated that glial fibrillary acidic protein and nestin exhibited dynamic expression in the rat hippocampus after permanent ligation of bilateral common carotid arteries. This finding suggests that dynamic alterations in protein expression play an important role in the pathogenesis of vascular dementia.展开更多
AIM： To characterize whether a glaucoma model with chronic elevation of the intraocular pressure （IOP） was able to be induced by anterior chamber injection of microbeads in rabbits.METHODS： In order to screen the ...AIM： To characterize whether a glaucoma model with chronic elevation of the intraocular pressure （IOP） was able to be induced by anterior chamber injection of microbeads in rabbits.METHODS： In order to screen the optimal dose of microbead injection, IOP was measured every 3d for 4wk using handheld applanation tonometer after a single intracameral injection of 10 μL, 25 μL, 50 μL or 100 μL microbeads （5×10^6 beads/mL; n=6/group） in New Zealand White rabbits. To prolong IOP elevation, two intracameral injections of 50 μL microbeads or phosphate buffer saline （PBS） were made respectively at days 0 and 21 （n=24/group）. The fellow eye was not treated. At 5wk after the second injection of microbeads or PBS, bright-field microscopy and transmission electron microscopy （TEM） were used to assess the changes in the retina. The expression of glial fibrillary acidic protein （GFAP） in the retina was evaluated by immunofluorescence, quantitative real-time polymerase chain reaction and Western blot at 5wk after the second injection of microbeads.RESULTS： Following a single intracameral injection of 10 μL, 25 μL, 50 μL or 100 μL microbead, IOP levels showed a gradual increase and a later decrease over a 4wk period after a single injection of microbead into the anterior chamber of rabbits. A peak IOP was observed at day 15 after injection. No significant difference in peak value of IOP was found between 10 μL and 25 μL groups （17.13±1.25 mm Hg vs 17.63±0.74 mm Hg; P=0.346）. The peak value of IOP from 50 μL group （23.25±1.16 mm Hg） was significantly higher than 10 μL and 25 μL groups （all P〈0.05）. Administration of 100 μL microbead solution （23.00±0.93 mm Hg） did not lead to a significant increase in IOP compared to the 50 μL group （P=0.64）. A prolonged elevated IOP duration up to 8wk was achieved by administering two injections of 50 μL microbeads （20.48±1.21 mm Hg vs 13.60±0.90 mm Hg in PBS-injected group; P〈0.05）. The bright-field and TEM were used to assess the changes of retinal ganglion cells （RGCs）. Compared with PBS-injected group, the extended IOP elevation was associated with the degeneration of optic nerve, the reduction of RGC axons （47.16%, P〈0.05） and the increased GFAP expression in the retina （4.74±1.10 vs 1.00±0.46, P〈0.05）.CONCLUSION： Two injections of microbeads into the ocular anterior chamber of rabbits lead to a prolonged IOP elevation which results in structural abnormality as well as loss in RGCs and their axons without observable ocular structural damage or inflammatory response. We have therefore established a novel and practical model of experimental glaucoma in rabbits.展开更多
Objective: To investigate the distribution and contents of vimentin(Vim) and glial fibrillary acidic protein(GFAP) immunoreactivities in the central nervous system(CNS)of normal newborn, adult and aged rats.Methods: I...Objective: To investigate the distribution and contents of vimentin(Vim) and glial fibrillary acidic protein(GFAP) immunoreactivities in the central nervous system(CNS)of normal newborn, adult and aged rats.Methods: In this study, thirty healthy and normal Sprague–Dawley rats were simply classified into three groups: Newborn(7 days aged), adult(5 months aged) and aged(24 months aged) rats. Brains and spinal cord were dissected and cut into frozen sections. The expression of Vim and GFAP in CNS were detected by confocal immunofluorescence.Results: In each group, Vim was expressed in all the regions of CNS including the hippocampal, cerebral cortex, the third ventricle and spinal cord, and the expression was highest in neuron-like cell of newborn rats, while Vim was mainly expressed in cell bodies in adult and aged rats. GFAP was expressed in all the regions of CNS including the hippocampal, cerebral cortex, the third ventricle and spinal cord, and the expression was in astrocytes of aged rats. In the third ventricle, Vim was detected in all groups, and only observed in neuron-like cells of newborn. Meanwhile, the GFAP expression showed no significant differences between adult and aged rats in this region. The co-localization of Vim and GFAP were mainly observed in hippocampus and cerebral cortex of newborn,but this co-localization was found in the third ventricle of the rats in all groups.Conclusion: Our data demonstrate for the first time that the expression of Vim and GFAP in the rat's CNS during development. This data may provide a foundation for the further mechanistic studies of these two main intermediate filaments during development of CNS.展开更多
BACKGROUND： Patients with type-2 diabetes mellitus exhibit higher levels of plasma endothelin-1 （ET-1）. However, very few reports exist regarding altered endothelin-3 （ET-3） and ET-1 concentrations in brain tissu...BACKGROUND： Patients with type-2 diabetes mellitus exhibit higher levels of plasma endothelin-1 （ET-1）. However, very few reports exist regarding altered endothelin-3 （ET-3） and ET-1 concentrations in brain tissue. OBJECTIVE： To observe expression changes of ET-3 and glial fibrillary acidic protein （GFAP） in the frontal and parietal cortex of type-2 diabetic mice following ischemia-reperfusion injury, with various reperfusion durations. DESIGN, TIME AND SETTING： Randomized controlled animal study. The experiment was conducted in the Xiangya Medical College of Central South University and the Third Xiangya Hospital between February 2002 and January 2003. MATERIALS： Sixty-six, adult, male, Kunming mice, weighing （30 ± 5） g, as well as rabbit anti-ET-3 polyclonal and rabbit anti-GFAP polyclonal antibodies, were provided by the Neurobiology Institute of Second Military Medical University in Japan. METHODS： Sixty-six mice were randomly divided into five groups： diabetes mellitus （DM, n = 6）, diabetes mellitus with ischemia-reperfusion （DM/IR, n = 24）, ischemia-reperfusion （IR, n = 24）, sham operation （SO, n = 6）, and control （n = 6）. MAIN OUTCOME MEASURES： Following ischemia-reperfusion for 1, 3, 5, and 10 days, respectively, expression of ET- 3 and GFAP was immunohistochemically measured in the frontal and parietal cortex. RESULTS： All 66 mice were included in the final result analysis. In the IR and DM/IR groups, ET-3- and GFAP-positive neurons increased in the frontal and parietal cortex in response to one day reperfusion, peaked at five days, and decreased at 10 days. ET-3 and GFAP expression was significantly greater in the DM/IR group after reperfusion for 1 day compared to the IR group. However, at other time points, there were no significant differences between the two groups. CONCLUSION： Brain ischemia-reperfusion injury results in overexpression of ET-3 and activation of astrocytes. Diabetes increases the number of ET-3- and GFAP-positive astrocytes in brain tissue of ischemia-reperfusion mice with the same reperfusion duration.展开更多
The present results demonstrated that in an adult rat model of permanent middle cerebral artery occlusion （pMCAO）, pretreatment with bilobalide reduced brain water content and infarct area, down-regulated aquaporin ...The present results demonstrated that in an adult rat model of permanent middle cerebral artery occlusion （pMCAO）, pretreatment with bilobalide reduced brain water content and infarct area, down-regulated aquaporin 1, 4 mRNA expression in brain edema tissue, then inhibited their synthesis in the striatum, in particular at the early stage of ischemia （at 8 hours after pMCAO）, inhibited glial fibrillary acidic protein expression, and lightened reactive gliosis. These data sug-gest that bilobalide attenuates brain edema formation due to reduced expression of aquaporins.展开更多
Objective To study the ex pr ession of Nestin and glial fibrillary acidic protein (GFAP) in different period after spinal injury in adult rats. Methods Animal moels were cr eated by artery clamp. Expression of Nest...Objective To study the ex pr ession of Nestin and glial fibrillary acidic protein (GFAP) in different period after spinal injury in adult rats. Methods Animal moels were cr eated by artery clamp. Expression of Nestin and GFAP in different period (1,3,5d ays;1-8 weeks) and different area(injury locus and its surrounding tissue ) afte r spinal injury were observed pathologicaly using immunofluorescence and LeicaQ5 00IW imaging processing system. Results There was expression of Nestin and GFAP in injured area 1 day after injury.The expression increased not only in in injured area but its sourrounding 3-7 days later and gradually got t o peak value. As the time went on, expression of Nestin and GFAP dereased. Conclusion Spinal injury can induce the expression of Nestin. Nerve stem cell has response to spinal injury. There is positive correlation between e xpression of Nestin and hyperplasia of reactivity astrocyte. Nerve stem cell may be invovled in the repair of central nervous system (CNS).展开更多
Objective：To explore the effects and anti-depression mechanisms of Kaixin Jieyu Decoction（开心解郁汤,KJD）.Methods：The rat vascular depression（VD） model was established by ligation of bilateral common carotid art...Objective：To explore the effects and anti-depression mechanisms of Kaixin Jieyu Decoction（开心解郁汤,KJD）.Methods：The rat vascular depression（VD） model was established by ligation of bilateral common carotid arteries（LBCCA） combined with chronic unpredictable mild stress（CUMS）.Forty Wistar rats were randomly divided into sham,VD model,VD ＋ high-dose KJD[15.4 g/（kg·d） of crude drug],VD ＋ medium-dose KJD[7.7 g/（kg·d） of crude drug],and VD ＋ fluoxetine[2.4 mg/（kg·d）]groups（r〉=8 in each group）,and the treatments lasted for 21 days.Changes of behavior and hippocampus pathology were observed.The level of glial fibrillary acidic protein（GFAP）protein and mRNA in hippocampus was detected respectively by immunohistochemistry and real-time polymerase chain reaction.Results：Compared with the sham group,rats in model group showed a variety of behavioral obstacles,including a significant reduction in sucrose consumption percentage,horizontal and vertical activity scores in open-field tests（P〈0.05 or P〈0.01）,pathological damage like neuronal degeneration,necrosis,and a significant decrease of GFAP protein and mRNA in hippocampus（P〈0.01）;compared with the model group,rats in the high-dose KJD group,medium-dose KJD group and fluoxetine group obtained notable higher behavioral scores,and pathological injury lessened in hippocampus with a increased expression of GFAP protein and mRNA（P〈0.05 or P〈0.01）;compared with the medium-dose KJD group and fluoxetine group,GFAP mRNA in highdose KJD group expressed higer（P〈0.05）.Conclusion：LBCCA combined with CUMS may cause depression-like behavioral changes resulting in the VD model of rats whose depression state can be ameliorated by KJD,and the mechanism of cerebral protection is related possibly with promoting expression of GFAP in hippocampus.展开更多
OBJECTIVE: To investigate the effects of basic fibroblast growth factor (bFGF) on the expression of glial fibrillary acidic protein (GFAP) after tractive spinal cord injury in rats and to explore the recovery of spina...OBJECTIVE: To investigate the effects of basic fibroblast growth factor (bFGF) on the expression of glial fibrillary acidic protein (GFAP) after tractive spinal cord injury in rats and to explore the recovery of spinal cord function. METHODS: The rats were subjected to tractive spinal cord injury at T13-L2. Cortical somatosensory-evoked potential (CSEP) was closely monitored and when P1-N1 wave amplitude decreased to 70% of that before operation, a small-bore catheter was inserted below the injured plane through subarachnoid cavity. In the treatment groups, 20 microl of bFGF solution (containing 20 microg of bFGF) was injected through the catheter right after the operation and 1, 2, 3, 4, 8, 12 and 24 h postoperatively. In the control group, same volume of normal saline was injected and every four rats were killed at 1, 4, 7, 14 and 21 d after the operation. Combined behavior score (CBS) and electro-physiological examination were adopted to evaluate function recovery. Expression of GFAP was observed by immuno-histochemical staining and was analyzed quantitatively by computer image analysis. RESULTS: There was statistically significant difference in GFAP-positive cells between bFGF treatment group and the control group (P展开更多
Multivariate modeling has demonstrated that the proliferation index （PI） of tumor cells is one of the strongest prognostic factors related to the survival of patients with astrocytic tumors. Studies have indicated t...Multivariate modeling has demonstrated that the proliferation index （PI） of tumor cells is one of the strongest prognostic factors related to the survival of patients with astrocytic tumors. Studies have indicated that the glioma regenerative cells derived from nestin-positive （N^＋） cells after chemotherapy. Early removal of N^＋cells can block the malignant progress of tumor.2 However, few studies compared the PI between N^＋cells and glial fibrillary acidic protein （GFAP）-positive （GFAP^＋） cells in human astrocytic tumors. In the present study, we investigated the distribution and proliferation ofN^＋cells and GFAP^＋ cells in human astrocytic tumors to clarify the role these cells play in the cytopathology of these tumors.展开更多
Background Muller cells in the mammalian retina normally express low levels of glial fibrillary acidic protein （GFAP）; however, its expression is upregulated in response to the loss of retinal neurons. The change in...Background Muller cells in the mammalian retina normally express low levels of glial fibrillary acidic protein （GFAP）; however, its expression is upregulated in response to the loss of retinal neurons. The change in expression of GFAP is one of the earliest indicators of retinal damage and is correlated with the time course of disease. The aim of this study was to investigate the time course of degeneration and the expression of GFAP in the retina of mer knockout mice. Methods A total of 30 mer knockout mice, aged from 15-20 days to 1 year and 32 age-matched wild type mice as controls were tested. Immunohistochemistry was used to show the expression of GFAP in the central and peripheral retina of mer knockout and control mice at postnatal age of 15 days （P15d）, 20 days （P20d）, 4 weeks （P4w）, 6 weeks （P6w）, 8 weeks （P8w）, 3 months （P3m）, 6 months （P6m） and 1 years （P1y）.Results The expression of GFAP in the central and peripheral retina of wild type mice was limited to the retinal ganglion cell and nerve fiber layers. In the central retina of mer knockout mice, GFAP expression was upregulated at P4w and GFAP immunolabelling penetrates across the entire thickness of the retina at P8w; whereas in the peripheral retina, the GFAP expression was upregulated at P20d and GFAP immunolabelling penetrates the entire retina after P4w. Conclusions Increased expression of GFAP in Muller cells of mer knockout mice occur at P20d in the peripheral retina and P4w in the central retina. GFAP expression in Muller cells appears to be a secondary response to the loss of retinal neurons. Increased expression of GFAP may occur prior to any detectable morphological changes in the retina. This study suggests that the loss of retinal neurons may begin in the early stages of retinitis pigmentosa, prior to the discovery of any morphological changes in the retina.展开更多
Background:Astrocytes play an essential role in neuroinflammation and are involved in the pathogenesis of neurodenegerative diseases.Studies of glial fibrillary acidic protein(GFAP),an astrocytic damage marker,may hel...Background:Astrocytes play an essential role in neuroinflammation and are involved in the pathogenesis of neurodenegerative diseases.Studies of glial fibrillary acidic protein(GFAP),an astrocytic damage marker,may help advance our understanding of different neurodegenerative diseases.In this study,we investigated the diagnostic performance of plasma GFAP(pGFAP),plasma neurofilament light chain(pNfL)and their combination for frontotemporal dementia(FTD)and Alzheimer's disease(AD)and their clinical utility in predicting disease progression.Methods:pGFAP and pNfL concentrations were measured in 72 FTD,56 AD and 83 cognitively normal(CN)participants using the Single Molecule Array technology.Of the 211 participants,199 underwent cerebrospinal(CSF)analysis and 122 had magnetic resonance imaging.We compared cross-sectional biomarker levels between groups,studied their diagnostic performance and assessed correlation between CSF biomarkers,cognitive performance and cortical thickness.The prognostic performance was investigated,analyzing cognitive decline through group comparisons by tertile.Results:Unlike pNfL,which was increased similarly in both clinical groups,pGFAP was increased in FTD but lower than in AD(all P<0.01).Combination of both plasma markers improved the diagnostic performance to discriminate FTD from AD(area under the curve[AUC]:combination 0.78;pGFAP 0.7;pNfL 0.61,all P<0.05).In FTD,pGFAP correlated with cognition,CSF and plasma NfL,and cortical thickness(all P<0.05).The higher tertile of pGFAP was associated with greater change in MMSE score and poor cognitive outcome during follow-up both in FTD(1.40 points annually,hazard ratio[HR]3.82,P<0.005)and in AD(1.20 points annually,HR 2.26,P<0.005).Conclusions:pGFAP and pNfL levels differ in FTD and AD;and their combination is useful for distinguishing between the two diseases.pGFAP could also be used to track disease severity and predict greater cognitive decline during follow-up in patients with FTD.展开更多
基金Supported by Hebei Medical Science Research Project,No.20220648。
文摘BACKGROUND Brain gliomas are malignant tumors with high postoperative recurrence rates.Early prediction of prognosis using specific indicators is of great significance.AIM To assess changes in ubiquitin carboxy-terminal hydrolase L1(UCH-L1)and glial fibrillary acidic protein(GFAP)levels in patients with glioma pre-and postoperatively.METHODS Between June 2018 and June 2021,91 patients with gliomas who underwent surgery at our hospital were enrolled in the glioma group.Sixty healthy volunteers were included in the control group.Serum UCH-L1 and GFAP levels were measured in peripheral blood collected from patients with glioma before and 3 d after surgery.UCH-L1 and GFAP levels in patients with glioma with different clinicopathological characteristics were compared before and after surgery.The patients were followed-up until February 2022.Postoperative glioma recurrence was recorded to determine the serum UCH-L1 and GFAP levels,which could assist in predicting postoperative glioma recurrence.RESULTS UCH-L1 and GFAP levels in patients with glioma decreased significantly 3 d after surgery compared to those before therapy(P<0.05).However,UCH-L1 and GFAP levels in the glioma group were significantly higher than those in the control group before and after surgery(P<0.05).There were no statistically significant differences in preoperative serum UCH-L1 and GFAP levels among patients with glioma according to sex,age,pathological type,tumor location,or number of lesions(P>0.05).Serum UCH-L1 and GFAP levels were significantly lower in the patients with WHO grade I-II tumors than in those with gradeⅢ-IV tumors(P<0.05).Serum UCH-L1 and GFAP levels were lower in the patients with tumor diameter≤5 cm than in those with diameter>5 cm,in which the differences were statistically significant(P<0.05).Glioma recurred in 22 patients.The preoperative and 3-d postoperative serum UCH-L1 and GFAP levels were significantly higher in the recurrence group than these in the non-recurrence group(P<0.05).Receiver operating characteristic curves were plotted.The areas under the curves of preoperative serum UCH-L1 and GFAP levels for predicting postoperative glioma recurrence were 0.785 and 0.775,respectively.However,the efficacy of serum UCH-L1 and GFAP levels 3 d after surgery in predicting postoperative glioma recurrence was slightly lower compared with their preoperative levels.CONCLUSION UCH-L1 and GFAP efficiently reflected the development and recurrence of gliomas and could be used as potential indicators for the recurrence and prognosis of glioma.
基金the National Natural Science Foundation of China (No. 30500189)
文摘Objective The present study aimed to explore the role of P2Y1 receptor in glial fibrillary acidic protein （GFAP） production and glial cell line-derived neurotrophic factor （GDNF） secretion of astrocytes under ischemic insult and the related signaling pathways. Methods Using transient right middle cerebral artery occlusion （tMCAO） and oxygen-glucose-serum deprivation for 2 h as the model of ischemic injury in vivo and in vitro, immunofluorescence, quantitative real-time reverse transcription-polymerase chain reaction （RT-PCR）, Western blotting, enzyme linked immunosorbent assay （ELISA） were used to investigate location of P2Y1 receptor and GDNF, the expression of GFAP and GDNF, and the changes of signaling molecules. Results Blockage of P2Y1 receptor with the selective antagonist N^6-methyl-2′-deoxyadenosine 3′,5′-bisphosphate diammonium （MRS2179） reduced GFAP production and increased GDNF production in the antagonist group as compared with simple ischemic group both in vivo and in vitro. Oxygen-glucose-serum deprivation and blockage of P2Y1 receptor caused elevation of phosphorylated Akt and cAMP response element binding protein （CREB）, and reduction of phosphorylated Janus kinase2 （JAK2） and signal transducer and activator of transcription3 （STAT3, Ser727）. After blockage of P2Y1 receptor and deprivation of oxygen-glucose-serum, AG490 （inhibitor of JAK2） reduced phosphorylation of STAT3 （Ser727） as well as expression of GFAP; LY294002, an inhibitor of phosphatidylinositol 3-kinase （PI3-K）, decreased phosphorylation of Akt and CREB; the inhibitor of mitogen-activated protein kinase kinase 1/2 （MEK 1/2） U0126, an important molecule of Ras/extracellular signal- regulated kinase （ERK） signaling pathway, decreased the phosphorylation of JAK2, STAT3 （Ser727）, Akt and CREB. Conclusion These results suggest that P2Y1 receptor plays a role in the production of GFAP and GDNF in astrocytes under transient ischemic condition and the related signaling pathways may be JAK2/STAT3 and PI3-K/Akt/CREB, respectively, and that crosstalk probably exists between them.
基金This study was funded by the National Natural Science Foundation of China,No.81470200(to XJR).
文摘Electroacupuncture(EA)has been shown to reduce blood lipid level and improve cerebral ischemia in rats with hyperlipemia complicated by cerebral ischemia.However,there are few studies on the results and mechanism of the effect of EA in reducing blood lipid level or promoting neural repair after stroke in hyperlipidemic subjects.In this study,EA was applied to a rat model of hyperlipidemia and middle cerebral artery thrombosis and the condition of neurons and astrocytes after hippocampal injury was assessed.Except for the normal group,rats in other groups were fed a high-fat diet throughout the whole experiment.Hyperlipidemia models were established in rats fed a high-fat diet for 6 weeks.Middle cerebral artery thrombus models were induced by pasting 50%FeCl3 filter paper on the left middle cerebral artery for 20 minutes on day 50 as the model group.EA1 group rats received EA at bilateral ST40(Fenglong)for 7 days before the thrombosis.Rats in the EA1 and EA2 groups received EA at GV20(Baihui)and bilateral ST40 for 14 days after model establishment.Neuronal health was assessed by hematoxylin-eosin staining in the brain.Hyperlipidemia was assessed by biochemical methods that measured total cholesterol,triglyceride,low-density lipoprotein and high-density lipoprotein in blood sera.Behavioral analysis was used to confirm the establishment of the model.Immunohistochemical methods were used to detect the expression of glial fibrillary acidic protein and nerve growth factor in the hippocampal CA1 region.The results demonstrated that,compared with the model group,blood lipid levels significantly decreased,glial fibrillary acidic protein immunoreactivity was significantly weakened and nerve growth factor immunoreactivity was significantly enhanced in the EA1 and EA2 groups.The repair effect was superior in the EA1 group than in the EA2 group.These findings confirm that EA can reduce blood lipid,inhibit glial fibrillary acidic protein expression and promote nerve growth factor expression in the hippocampal CA1 region after hyperlipidemia and middle cerebral artery thrombosis.All experimental procedures and protocols were approved by the Animal Use and Management Committee of Beijing University of Chinese Medicine,China(approval No.BUCM-3-2018022802-1002)on April 12,2018.
基金Supported by Special Scientific Research Program of Shaanxi Provincial Education Department(No.16JK1665)
文摘AIM：To assess the expression of nestin and glial fibrillary acidic protein（GFAP）in rat retina after optic nerve transection.METHODS：Rats were randomly divided into normal control group,sham group and operation group,and used for establishing an animal model of optic nerve transection.Retinal specimen of each group was collected at 3,48h,7and 14d postoperative.Nestin and GFAP expressions on sagittal sections were analyzed by immunohistochemical staining,and protein extraction was analyzed by Western blot.RESULTS：Immunohistochemical analysis showed that nestin positive staining was rarely detected in normal control group and sham group,while sham group showed weak positive staining at 3h postoperative,the reaction gradually increased at 48h postoperative,and reached its maximum at 7d postoperative,and then decreased at 14d postoperative.Compared to the expression of GFAP,there was not statistically significant obvious difference among three groups（P〉0.05）.Result of Western blot method was consistent with that of immunohistochemical method.CONCLUSION：The expression of nestin increased in a time dependent fashion in Müller cells of retina following optic nerve transection,which was statistically significant,but there was no obvious difference in GFAP expression.The results indicate that an increase in colloid synthesis in retina following optic nerve transection can improve the retinal neurons’environment.
基金supported by Brazilian funding agencies CNPq,CAPES and FAPERGS
文摘Emerging evidence has suggested global histone H4 acetylation status plays an important role in neural plasticity. For instance, the imbalance of this epigenetic marker has been hypothesized as a key factor for the development and progression of several neurological diseases. Likewise, astrocytic reactivity-a wellknown process that markedly influences the tissue remodeling after a central nervous system injury-is crucial for tissue remodeling after spinal cord injury（SCI）. However, the linkage between the above-mentioned mechanisms after SCI remains poorly understood. We sought to investigate the relation between both glial fibrillary acidic protein（GFAP） and S100 calcium-binding protein B（S100B）（astrocytic reactivity classical markers） and global histone H4 acetylation levels. Sixty-one male Wistar rats（aged ~3 months） were divided into the following groups： sham; 6 hours post-SCI; 24 hours post-SCI; 48 hours post-SCI; 72 hours post-SCI; and 7 days post-SCI. The results suggested that GFAP, but not S100B was associated with global histone H4 acetylation levels. Moreover, global histone H4 acetylation levels exhibited a complex pattern after SCI, encompassing at least three clearly defined phases（first phase： no changes in the 6, 24 and 48 hours post-SCI groups; second phase： increased levels in the 72 hours post-SCI group; and a third phase： return to levels similar to control in the 7 days post-SCI group）. Overall, these findings suggest global H4 acetylation levels exhibit distinct patterns of expression during the first week post-SCI, which may be associated with GFAP levels in the perilesional tissue. Current data encourage studies using H4 acetylation as a possible biomarker for tissue remodeling after spinal cord injury.
基金sponsored by the National Natural Science Foundation of China, No. 30740035Key Scientific and Technological Project of Sichuan Province, No. 05SG1672
文摘The present study analyzed the effects of ethanol extracts of scorpion on epilepsy prevention and hippocampal expression of glial fibrillary acidic protein in a lithium chloride-pilocarpine epileptic rat model. Results were subsequently compared with valproic acid. Results showed gradually- increased hippocampal glial fibrillary acidic protein expression following model establishment; glial fibrillary acidic protein mRNA expression was significantly increased at 3 days, reached a peak at 7 days, and then gradually decreased thereafter. Ethanol extracts of scorpion doses of 580 and 1 160 mg/kg, as well as 120 mg/kg valproic acid, led to a decreased number of glial fibrillary acidic protein-positive cells and glial fibrillary acidic protein mRNA expression, as well as decreased seizure grades and frequency of spontaneously recurrent seizures. The effects of 1 160 mg/kg ethanol extracts of scorpion were equal to those of 120 mg/kg valproic acid. These results suggested that the anti-epileptic effect of ethanol extracts of scorpion were associated with decreased hippocampal glial fibrillary acidic protein expression in a rat model of lithium chlofide-pilocarpine induced epilepsy.
基金Supported by:the Science and Technology Development Program of Sichuan Provincial Science and Technology Department, No 05SG022-013
文摘BACKGROUND： Gamma-aminobutyric acid transporter plays an important role in gamma-aminobutyric acid metabolism, and is highly associated with epilepsy seizures. Pathologically, astrocytes release active substances that alter neuronal excitability, and it has been demonstrated that astrocytes play a role in epileptic seizures. OBJECTIVE： To observe changes in gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression in the hippocampus and cortex of the temporal lobe in rats with pentylenetetrazol-induced chronic epilepsy. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment was performed at the Department of Neurobiology, Third Military University of Chinese PLA between January 2006 and December 2007. MATERIALS： Pentylenetetrazol was purchased from Sigma, USA; rabbit anti-rat gammaaminobutyric acid transporter 1 and glial fibrillary acidic protein were from Chemicon, USA. METHODS： A total of 40 Sprague Dawley rats were divided into model and control groups. Rat models of chronic epilepsy were created by pentylenetetrazol kindling, and were subdivided into 3-, 7-, and 14-day kindling subgroups. MAIN OUTCOME MEASURES： Gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression, as well as the number of positive cells in the hippocampus and cortex of temporal lobe of rats, were determined by immunohistochemistry and Western blot analyses. RESULTS： Compared with the control group, the number of gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein -positive cells in the hippocampus and cortex of rats with pentylenetetrazol-induced epilepsy significantly increased, gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression increased after 3 days of kindling, reached a peak on day 7, and remained at elevated levels at day 14 （P〈 0.05）. CONCLUSION： Astrocytic activation and gamma-aminobutyric acid transporter 1 overexpression may contribute to pentylenetetrazol-induced epilepsy.
文摘Diverse neurotoxic insults result in proliferation and hypertrophy of astrocytes. The hallmark of this response is enhanced expression of the major intermediate filament protein of astrocytes, glial fibrillary acidic protein (GFAP). These observations suggest that GFAP may be a useful biomarker of neurotoxicity. To investigate this possibility, we administered prototype neurotoxicants to experimental animals and assessed the effects of these agents on the tissue content of GFAP, as determined by radioimmunoassay. A review of the background, design, and results of these experiments are presented in this paper. Our findings indicate that GFAP is a sensitive and specific biomarker of neurotoxicity.
基金the National Natural Science Foundation of China, No. 30973154Chongqing Science and Technology Commission Foundation, No. 2009BB5270Chongqing Municipal Education Com-mission Foundation, No. KJ090301
文摘Astrocytes can alter their appearance and become reactive following chronic cerebral ischemia. In the present study, a rat model of chronic cerebral ischemia was treated with 50 and 100 mg/kg curcumin. Results showed that pathological changes of neuronal injury in hippocampal CA1 area of rats induced by chronic cerebral ischemia were attenuated, as well as upregulated expression of glial fibriliary acidic protein and nestin, in a dose-dependent manner.
基金the National Natural Science Foundation of China, No. 30973154Chongqing Science and Technology Commission Foundation, No. 2009BB5270Chongqing Municipal Education Commission Foundation, No. KJ090301
文摘Vascular dementia produced by permanent ligation of bilateral common carotid arteries involves progressive deterioration of intellectual and cognitive function in rats, which are closely associated with the hippocampus. This study used immunohistochemical analysis to detect the expression of glial fibrillary acidic protein and nestin in the hippocampus in a vascular dementia model. The results revealed that both glial fibrillary acidic protein and nestin expression were increased 1 day after permanent ligation of the bilateral common carotid arteries, compared with a sham-operated group. The expression of glial fibrillary acidic protein peaked at 7 days post-surgery. The expression of nestin was a little weaker than that of glial fibrillary acidic protein, and peaked at 14 days （P 〈 0.01）. The expression of both proteins slightly decreased at 21 and 28 days, accompanied by recovery of cerebral blood flow. In conclusion, this study demonstrated that glial fibrillary acidic protein and nestin exhibited dynamic expression in the rat hippocampus after permanent ligation of bilateral common carotid arteries. This finding suggests that dynamic alterations in protein expression play an important role in the pathogenesis of vascular dementia.
基金Supported by Shenzhen Science and Technology Innovation Committee in China(No.JCYJ20120831154554508No.JCYJ20140415174819509+1 种基金No.GJHZ20160229170608241)Medical Science and Technology Research Fund Project in Guangdong Province(No.A2015315)
文摘AIM： To characterize whether a glaucoma model with chronic elevation of the intraocular pressure （IOP） was able to be induced by anterior chamber injection of microbeads in rabbits.METHODS： In order to screen the optimal dose of microbead injection, IOP was measured every 3d for 4wk using handheld applanation tonometer after a single intracameral injection of 10 μL, 25 μL, 50 μL or 100 μL microbeads （5×10^6 beads/mL; n=6/group） in New Zealand White rabbits. To prolong IOP elevation, two intracameral injections of 50 μL microbeads or phosphate buffer saline （PBS） were made respectively at days 0 and 21 （n=24/group）. The fellow eye was not treated. At 5wk after the second injection of microbeads or PBS, bright-field microscopy and transmission electron microscopy （TEM） were used to assess the changes in the retina. The expression of glial fibrillary acidic protein （GFAP） in the retina was evaluated by immunofluorescence, quantitative real-time polymerase chain reaction and Western blot at 5wk after the second injection of microbeads.RESULTS： Following a single intracameral injection of 10 μL, 25 μL, 50 μL or 100 μL microbead, IOP levels showed a gradual increase and a later decrease over a 4wk period after a single injection of microbead into the anterior chamber of rabbits. A peak IOP was observed at day 15 after injection. No significant difference in peak value of IOP was found between 10 μL and 25 μL groups （17.13±1.25 mm Hg vs 17.63±0.74 mm Hg; P=0.346）. The peak value of IOP from 50 μL group （23.25±1.16 mm Hg） was significantly higher than 10 μL and 25 μL groups （all P〈0.05）. Administration of 100 μL microbead solution （23.00±0.93 mm Hg） did not lead to a significant increase in IOP compared to the 50 μL group （P=0.64）. A prolonged elevated IOP duration up to 8wk was achieved by administering two injections of 50 μL microbeads （20.48±1.21 mm Hg vs 13.60±0.90 mm Hg in PBS-injected group; P〈0.05）. The bright-field and TEM were used to assess the changes of retinal ganglion cells （RGCs）. Compared with PBS-injected group, the extended IOP elevation was associated with the degeneration of optic nerve, the reduction of RGC axons （47.16%, P〈0.05） and the increased GFAP expression in the retina （4.74±1.10 vs 1.00±0.46, P〈0.05）.CONCLUSION： Two injections of microbeads into the ocular anterior chamber of rabbits lead to a prolonged IOP elevation which results in structural abnormality as well as loss in RGCs and their axons without observable ocular structural damage or inflammatory response. We have therefore established a novel and practical model of experimental glaucoma in rabbits.
基金supported by National Natural Science Foundation of China(No:81500377)the Joint Special Fund between Yunnan Provincial Science and Technology Department and Kunming Medical University(No:2015FB009,2015FB153)Program for Students Innovation in Kunming Medical University
文摘Objective: To investigate the distribution and contents of vimentin(Vim) and glial fibrillary acidic protein(GFAP) immunoreactivities in the central nervous system(CNS)of normal newborn, adult and aged rats.Methods: In this study, thirty healthy and normal Sprague–Dawley rats were simply classified into three groups: Newborn(7 days aged), adult(5 months aged) and aged(24 months aged) rats. Brains and spinal cord were dissected and cut into frozen sections. The expression of Vim and GFAP in CNS were detected by confocal immunofluorescence.Results: In each group, Vim was expressed in all the regions of CNS including the hippocampal, cerebral cortex, the third ventricle and spinal cord, and the expression was highest in neuron-like cell of newborn rats, while Vim was mainly expressed in cell bodies in adult and aged rats. GFAP was expressed in all the regions of CNS including the hippocampal, cerebral cortex, the third ventricle and spinal cord, and the expression was in astrocytes of aged rats. In the third ventricle, Vim was detected in all groups, and only observed in neuron-like cells of newborn. Meanwhile, the GFAP expression showed no significant differences between adult and aged rats in this region. The co-localization of Vim and GFAP were mainly observed in hippocampus and cerebral cortex of newborn,but this co-localization was found in the third ventricle of the rats in all groups.Conclusion: Our data demonstrate for the first time that the expression of Vim and GFAP in the rat's CNS during development. This data may provide a foundation for the further mechanistic studies of these two main intermediate filaments during development of CNS.
文摘BACKGROUND： Patients with type-2 diabetes mellitus exhibit higher levels of plasma endothelin-1 （ET-1）. However, very few reports exist regarding altered endothelin-3 （ET-3） and ET-1 concentrations in brain tissue. OBJECTIVE： To observe expression changes of ET-3 and glial fibrillary acidic protein （GFAP） in the frontal and parietal cortex of type-2 diabetic mice following ischemia-reperfusion injury, with various reperfusion durations. DESIGN, TIME AND SETTING： Randomized controlled animal study. The experiment was conducted in the Xiangya Medical College of Central South University and the Third Xiangya Hospital between February 2002 and January 2003. MATERIALS： Sixty-six, adult, male, Kunming mice, weighing （30 ± 5） g, as well as rabbit anti-ET-3 polyclonal and rabbit anti-GFAP polyclonal antibodies, were provided by the Neurobiology Institute of Second Military Medical University in Japan. METHODS： Sixty-six mice were randomly divided into five groups： diabetes mellitus （DM, n = 6）, diabetes mellitus with ischemia-reperfusion （DM/IR, n = 24）, ischemia-reperfusion （IR, n = 24）, sham operation （SO, n = 6）, and control （n = 6）. MAIN OUTCOME MEASURES： Following ischemia-reperfusion for 1, 3, 5, and 10 days, respectively, expression of ET- 3 and GFAP was immunohistochemically measured in the frontal and parietal cortex. RESULTS： All 66 mice were included in the final result analysis. In the IR and DM/IR groups, ET-3- and GFAP-positive neurons increased in the frontal and parietal cortex in response to one day reperfusion, peaked at five days, and decreased at 10 days. ET-3 and GFAP expression was significantly greater in the DM/IR group after reperfusion for 1 day compared to the IR group. However, at other time points, there were no significant differences between the two groups. CONCLUSION： Brain ischemia-reperfusion injury results in overexpression of ET-3 and activation of astrocytes. Diabetes increases the number of ET-3- and GFAP-positive astrocytes in brain tissue of ischemia-reperfusion mice with the same reperfusion duration.
基金a Research Subject of General Hospital of Shenyang Military Area Command of Chinese PLA
文摘The present results demonstrated that in an adult rat model of permanent middle cerebral artery occlusion （pMCAO）, pretreatment with bilobalide reduced brain water content and infarct area, down-regulated aquaporin 1, 4 mRNA expression in brain edema tissue, then inhibited their synthesis in the striatum, in particular at the early stage of ischemia （at 8 hours after pMCAO）, inhibited glial fibrillary acidic protein expression, and lightened reactive gliosis. These data sug-gest that bilobalide attenuates brain edema formation due to reduced expression of aquaporins.
文摘Objective To study the ex pr ession of Nestin and glial fibrillary acidic protein (GFAP) in different period after spinal injury in adult rats. Methods Animal moels were cr eated by artery clamp. Expression of Nestin and GFAP in different period (1,3,5d ays;1-8 weeks) and different area(injury locus and its surrounding tissue ) afte r spinal injury were observed pathologicaly using immunofluorescence and LeicaQ5 00IW imaging processing system. Results There was expression of Nestin and GFAP in injured area 1 day after injury.The expression increased not only in in injured area but its sourrounding 3-7 days later and gradually got t o peak value. As the time went on, expression of Nestin and GFAP dereased. Conclusion Spinal injury can induce the expression of Nestin. Nerve stem cell has response to spinal injury. There is positive correlation between e xpression of Nestin and hyperplasia of reactivity astrocyte. Nerve stem cell may be invovled in the repair of central nervous system (CNS).
基金Supported by the National Natural Science Foundation of China(No.81072801 and 30672696)
文摘Objective：To explore the effects and anti-depression mechanisms of Kaixin Jieyu Decoction（开心解郁汤,KJD）.Methods：The rat vascular depression（VD） model was established by ligation of bilateral common carotid arteries（LBCCA） combined with chronic unpredictable mild stress（CUMS）.Forty Wistar rats were randomly divided into sham,VD model,VD ＋ high-dose KJD[15.4 g/（kg·d） of crude drug],VD ＋ medium-dose KJD[7.7 g/（kg·d） of crude drug],and VD ＋ fluoxetine[2.4 mg/（kg·d）]groups（r〉=8 in each group）,and the treatments lasted for 21 days.Changes of behavior and hippocampus pathology were observed.The level of glial fibrillary acidic protein（GFAP）protein and mRNA in hippocampus was detected respectively by immunohistochemistry and real-time polymerase chain reaction.Results：Compared with the sham group,rats in model group showed a variety of behavioral obstacles,including a significant reduction in sucrose consumption percentage,horizontal and vertical activity scores in open-field tests（P〈0.05 or P〈0.01）,pathological damage like neuronal degeneration,necrosis,and a significant decrease of GFAP protein and mRNA in hippocampus（P〈0.01）;compared with the model group,rats in the high-dose KJD group,medium-dose KJD group and fluoxetine group obtained notable higher behavioral scores,and pathological injury lessened in hippocampus with a increased expression of GFAP protein and mRNA（P〈0.05 or P〈0.01）;compared with the medium-dose KJD group and fluoxetine group,GFAP mRNA in highdose KJD group expressed higer（P〈0.05）.Conclusion：LBCCA combined with CUMS may cause depression-like behavioral changes resulting in the VD model of rats whose depression state can be ameliorated by KJD,and the mechanism of cerebral protection is related possibly with promoting expression of GFAP in hippocampus.
文摘OBJECTIVE: To investigate the effects of basic fibroblast growth factor (bFGF) on the expression of glial fibrillary acidic protein (GFAP) after tractive spinal cord injury in rats and to explore the recovery of spinal cord function. METHODS: The rats were subjected to tractive spinal cord injury at T13-L2. Cortical somatosensory-evoked potential (CSEP) was closely monitored and when P1-N1 wave amplitude decreased to 70% of that before operation, a small-bore catheter was inserted below the injured plane through subarachnoid cavity. In the treatment groups, 20 microl of bFGF solution (containing 20 microg of bFGF) was injected through the catheter right after the operation and 1, 2, 3, 4, 8, 12 and 24 h postoperatively. In the control group, same volume of normal saline was injected and every four rats were killed at 1, 4, 7, 14 and 21 d after the operation. Combined behavior score (CBS) and electro-physiological examination were adopted to evaluate function recovery. Expression of GFAP was observed by immuno-histochemical staining and was analyzed quantitatively by computer image analysis. RESULTS: There was statistically significant difference in GFAP-positive cells between bFGF treatment group and the control group (P
基金This study was supported by grants from the National Natural Science Foundation of China （No, 30973083）, the Science and Technology Commission, Fujian, China （No. 200710014）, and Science Research Foundation of Ministry of Health ＆ United Fujian Provincial Health and Education Project for Tackling the Key Research （No. WKJ2008- 2-45）.Acknowledgment： We thank Prof. Hu Zhijian of Fujian Medical University for assistance in data processing and statistical analysis.
文摘Multivariate modeling has demonstrated that the proliferation index （PI） of tumor cells is one of the strongest prognostic factors related to the survival of patients with astrocytic tumors. Studies have indicated that the glioma regenerative cells derived from nestin-positive （N^＋） cells after chemotherapy. Early removal of N^＋cells can block the malignant progress of tumor.2 However, few studies compared the PI between N^＋cells and glial fibrillary acidic protein （GFAP）-positive （GFAP^＋） cells in human astrocytic tumors. In the present study, we investigated the distribution and proliferation ofN^＋cells and GFAP^＋ cells in human astrocytic tumors to clarify the role these cells play in the cytopathology of these tumors.
基金This work was supported by the grants from the National Natural Science Foundation of China （No. 30571991 and 30672283）.Acknowledgements： The authors thank Dr. WANG Hai-kun of the Peking Union Medical College for animal keeping and breeding, Dr. LU Qing-xian and Dr. LU Qing-jun for the generous gift of animal models and their assistance in the work technique, Beijing Ophthalmology Institute for technical support.
文摘Background Muller cells in the mammalian retina normally express low levels of glial fibrillary acidic protein （GFAP）; however, its expression is upregulated in response to the loss of retinal neurons. The change in expression of GFAP is one of the earliest indicators of retinal damage and is correlated with the time course of disease. The aim of this study was to investigate the time course of degeneration and the expression of GFAP in the retina of mer knockout mice. Methods A total of 30 mer knockout mice, aged from 15-20 days to 1 year and 32 age-matched wild type mice as controls were tested. Immunohistochemistry was used to show the expression of GFAP in the central and peripheral retina of mer knockout and control mice at postnatal age of 15 days （P15d）, 20 days （P20d）, 4 weeks （P4w）, 6 weeks （P6w）, 8 weeks （P8w）, 3 months （P3m）, 6 months （P6m） and 1 years （P1y）.Results The expression of GFAP in the central and peripheral retina of wild type mice was limited to the retinal ganglion cell and nerve fiber layers. In the central retina of mer knockout mice, GFAP expression was upregulated at P4w and GFAP immunolabelling penetrates across the entire thickness of the retina at P8w; whereas in the peripheral retina, the GFAP expression was upregulated at P20d and GFAP immunolabelling penetrates the entire retina after P4w. Conclusions Increased expression of GFAP in Muller cells of mer knockout mice occur at P20d in the peripheral retina and P4w in the central retina. GFAP expression in Muller cells appears to be a secondary response to the loss of retinal neurons. Increased expression of GFAP may occur prior to any detectable morphological changes in the retina. This study suggests that the loss of retinal neurons may begin in the early stages of retinitis pigmentosa, prior to the discovery of any morphological changes in the retina.
基金supported by the Fondo de Investigaciones Sanitario(FIS)Institute de Salud Carlos III(P114/01126,P117/01019 and PI20/01473 to JF,PI13/01532 and PI16/01825 to RB,PI18/00335 to MCI,PI18/00435 and INT19/00016 to DA,PI17/01896 and AC19/00103to AL)+4 种基金the CIBERNED program(Program 1,Alzheimer Disease to AL)jointly funded by Fondo Europeo de Desarrollo Regional,Unión Europea,"Una manera de hacer Europa"supported by Generalitat de Catalunya(2017-SGR-547,SLT006/17/125 to DA,SLT006/17/119 to JF,SLT002/16/408 to AL)"MaratóTV3"foundation grants 20141210 to JF,044412 to RB and 20142610 to ALsupported by a grant from the Fundacio Bancaria La Caixa to RB(DABNI project).
文摘Background:Astrocytes play an essential role in neuroinflammation and are involved in the pathogenesis of neurodenegerative diseases.Studies of glial fibrillary acidic protein(GFAP),an astrocytic damage marker,may help advance our understanding of different neurodegenerative diseases.In this study,we investigated the diagnostic performance of plasma GFAP(pGFAP),plasma neurofilament light chain(pNfL)and their combination for frontotemporal dementia(FTD)and Alzheimer's disease(AD)and their clinical utility in predicting disease progression.Methods:pGFAP and pNfL concentrations were measured in 72 FTD,56 AD and 83 cognitively normal(CN)participants using the Single Molecule Array technology.Of the 211 participants,199 underwent cerebrospinal(CSF)analysis and 122 had magnetic resonance imaging.We compared cross-sectional biomarker levels between groups,studied their diagnostic performance and assessed correlation between CSF biomarkers,cognitive performance and cortical thickness.The prognostic performance was investigated,analyzing cognitive decline through group comparisons by tertile.Results:Unlike pNfL,which was increased similarly in both clinical groups,pGFAP was increased in FTD but lower than in AD(all P<0.01).Combination of both plasma markers improved the diagnostic performance to discriminate FTD from AD(area under the curve[AUC]:combination 0.78;pGFAP 0.7;pNfL 0.61,all P<0.05).In FTD,pGFAP correlated with cognition,CSF and plasma NfL,and cortical thickness(all P<0.05).The higher tertile of pGFAP was associated with greater change in MMSE score and poor cognitive outcome during follow-up both in FTD(1.40 points annually,hazard ratio[HR]3.82,P<0.005)and in AD(1.20 points annually,HR 2.26,P<0.005).Conclusions:pGFAP and pNfL levels differ in FTD and AD;and their combination is useful for distinguishing between the two diseases.pGFAP could also be used to track disease severity and predict greater cognitive decline during follow-up in patients with FTD.
