Glioblastomas are characterized by an aggressive local growth pattern, a marked degree of invasiveness and poor prognosis. Tumor invasiveness is facilitated by the increased activity of proteolytic enzymes which are i...Glioblastomas are characterized by an aggressive local growth pattern, a marked degree of invasiveness and poor prognosis. Tumor invasiveness is facilitated by the increased activity of proteolytic enzymes which are involved in destruction of the extracellular matrix of the surrounding healthy brain tissue. Elevated levels of matrix metalloproteinases(MMPs) were found in glioblastoma(GBM) cell-lines, as well as in GBM biopsies as compared with low-grade astrocytoma(LGA) and normal brain samples, indicating a role in malignant progression. A careful review of the available literature revealed that both the expression and role of several of the 23 human MMP proteins is controversely discussed and for some there are no data available at all. We therefore screened a panel of 15 LGA and 15 GBM biopsy samples for those MMPs for which there is either no, very limited or even contradictory dataavailable. Hence, this is the first complete compilation of the expression pattern of all 23 human MMPs in astrocytic tumors. This study will support a better understanding of the specific expression patterns and interaction of proteolytic enzymes in malignant human glioma and may provide additional starting points for targeted patient therapy.展开更多
After spinal cord injury(SCI),astrocytes gradually migrate to and surround the lesion,depositing chondroitin sulfate proteoglycan-rich extracellular matrix and forming astrocytic scar,which limits the spread of inflam...After spinal cord injury(SCI),astrocytes gradually migrate to and surround the lesion,depositing chondroitin sulfate proteoglycan-rich extracellular matrix and forming astrocytic scar,which limits the spread of inflammation but hinders axon regeneration.Meanwhile,microglia gradually accumulate at the lesion border to form microglial scar and can polarize to generate a pro-inflammatory M1 phenotype or an anti-inflammatory M2 phenotype.However,the effect of microglia polarization on astrocytes is unclear.Here,we found that both microglia(CX3 CR1^(+))and astrocytes(GFAP^(+))gathered at the lesion border at 14 days post-injury(dpi).The microglia accumulated along the inner border of and in direct contact with the astrocytes.M1-type microglia(i NOS^(+)CX3 CR1^(+))were primarily observed at 3 and 7 dpi,while M2-type microglia(Arg1^(+)CX3 CR1^(+))were present at larger numbers at 7 and 14 dpi.Transforming growth factor-β1(TGFβ1)was highly expressed in M1 microglia in vitro,consistent with strong expression of TGFβ1 by microglia in vivo at 3 and 7 dpi,when they primarily exhibited an M1 phenotype.Furthermore,conditioned media from M1-type microglia induced astrocytes to secrete chondroitin sulfate proteoglycan in vitro.This effect was eliminated by knocking down sex-determining region Y-box 9(SOX9)in astrocytes and could not be reversed by treatment with TGFβ1.Taken together,our results suggest that microglia undergo M1 polarization and express high levels of TGFβ1 at 3 and 7 dpi,and that M1-type microglia induce astrocytes to deposit chondroitin sulfate proteoglycan via the TGFβ1/SOX9 pathway.The study was approved by the Institutional Animal Care and Use Committee of Anhui Medical University,China(approval No.LLSC20160052)on March 1,2016.展开更多
Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However...Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.展开更多
Astrocytic Kir4.1 channels and spatial potassium buffering：Astrocytes play a crucial role in maintaining the structural and functional integrity of the brain,which includes formation of the blood-brain barrier,mainte...Astrocytic Kir4.1 channels and spatial potassium buffering：Astrocytes play a crucial role in maintaining the structural and functional integrity of the brain,which includes formation of the blood-brain barrier,maintenance of water and ion homeostasis,metabolism of neurotransmitters and secretion of various neuroactive molecules.展开更多
Background Our previous study confirmed that oligodendrogliomas had higher frequency of chromosome 1p/19q deletion. In order to improve the diagnostic criteria and to predict the prognosis of oligodendroglioma patient...Background Our previous study confirmed that oligodendrogliomas had higher frequency of chromosome 1p/19q deletion. In order to improve the diagnostic criteria and to predict the prognosis of oligodendroglioma patients, the status of chromosome 1 p/19q deletion, the methylation of O6-methylguanine-DNA methyltransferase （MGMT）, and the expression of p53 protein were evaluated and investigated in relation to patients＇ outcomes.Methods Methylation of MGMT in 73 cases was analyzed by nested methylation-specific PCR （MSP）. The levels of MGMT and p53 protein were tested with immunohistochemistry. Pearson＇s chi-square test and Fisher＇s exact test were used. Multivariate and Kaplan-Meier analysis were performed to determine patients＇ outcomes.Results Both oligodendrogliomas and astrocytic gliomas exhibited frequent methylation of MGMT. However, the results of MSP did not completely correspond to that of the immunohistochemical staining for MGMT. The expression of p53 protein was more frequently observed in patients without a 1 p or 19q deletion in anaplastic oligodendrogliomas （=0.032,0.025）. In low-grade oligodendrogliomas, methylation of MGMT was more frequent in patients with 1 p/19q deletion than in patients with 1p/19q intact （P=0.038）. Patients with oligodendrogliomas with 1p/19q loss of heterozygosity and p53-negative showed a longer progression-free survival.Conclusion Detection of chromosome 1p/19q status combined with p53 protein immunohistochemistry might be beneficial to improve the pathological diagnosis and to determine the prognosis of patients with oligodendrogliomas.展开更多
To explore the roles of astrocytes in the epileptogenesis, astrocytes and neurons were isolated, purified and cultured in vitro from cerebral cortex of rats. The astrocytes were activated by ciliary neurotrophic facto...To explore the roles of astrocytes in the epileptogenesis, astrocytes and neurons were isolated, purified and cultured in vitro from cerebral cortex of rats. The astrocytes were activated by ciliary neurotrophic factor (CNTF) and astrocytic conditioned medium (ACM) was collected to treat neurons for 4, 8 and 12 h. By using Western blot, the expression of calmodulin dependent protein kinase Ⅱ (CaMKⅡ), inducible nitric oxide synthase (iNOS) and adenylate cyclase (AC) was de- tected in neurons. The results showed that the expression of CaMKⅡ, iNOS and AC was increased significantly in the neurons treated with ACM from 4 h to 12 h (P<0.05), and that of iNOS and AC peaked at 8 h and 12 h respectively. It was suggested that there might be some epileptogenic factors in the ACM and such signal pathways as NOS-NO-cGMP, Ca2+?CaM-CaMKⅡ and AC-cAMP-PKA might take part in the signal transduction of epileptogenesis.展开更多
Dynamic structuring and functions of perisynaptic astrocytic processes and of the gap junction network within a single astrocyte are outlined. Motile perisynaptic astrocytic processes are generating microdomains. By c...Dynamic structuring and functions of perisynaptic astrocytic processes and of the gap junction network within a single astrocyte are outlined. Motile perisynaptic astrocytic processes are generating microdomains. By contacting and retracting of their endfeet an appropriate receptor pattern is selected that modulates the astrocytic receptor sheath for its activation by neurotransmitter substances, ions, transporters, etc. This synaptic information processing occurs in three distinct time scales of milliseconds to seconds, seconds to minutes, hours or longer. Simultaneously, the interconnecting gap junctions are activated by building a network within the astrocyte. Frequently activated gap junction cycles become embodied in gap junction plaques. The gap junction network formation and gap junction plaques are governed and controlled in the same time scales as synaptic information processing. Biomimetic computer systems may represent an alternative to limitations of brainphysiological research. The model proposed allows the interpretation of affective psychoses and schizophrenia as time disorders basically determined by a shortened, prolonged or lacking time scale of synaptic information processing.展开更多
In chronic schizophrenia, synaptic information processing is unbalanced, as shown in a model of glial-neuronal synaptic units, called tripartite synapses. The glial component of the synapse exerts a modifying function...In chronic schizophrenia, synaptic information processing is unbalanced, as shown in a model of glial-neuronal synaptic units, called tripartite synapses. The glial component of the synapse exerts a modifying function in neurotransmission since the astrocyte activated by neurotransmitters produces gliotransmitters that negatively feedback to the presynapse. It is hypothesized that in schizophrenia nonfunctional astrocytic receptors cannot be activated, thus losing their modulating function. This causes a generalization of information processing in the neuronal networks such that the brain is unable to distinguish between subjects and objects in the environment. Delusions, hallucinations and cognitive impairment occur on the behavioral level. In a model of a cholinergic tripartite synapse, it is shown that glial binding proteins modify neurotransmission by occupancy with cognate neurotransmitters temporarily turning off neurotransmission on the presynapse. Most recently, glial binding proteins have been engineered. It is proposed that the substitution of glial binding proteins may balance synaptic information processing in schizophrenia since these proteins exert a modulatory function comparable to functional astrocytic receptors. Rap- id technical developments may enable this novel treatment approach in schizophrenia.展开更多
Background:Astrocytes become reactive following many types of CNS injuries.Excessive astrogliosis is detrimental and contributes to neuronal damage.We sought to determine whether inhibition of cell cycle could decreas...Background:Astrocytes become reactive following many types of CNS injuries.Excessive astrogliosis is detrimental and contributes to neuronal damage.We sought to determine whether inhibition of cell cycle could decrease the proliferation of astroglial cells and therefore reduce excessive gliosis and glial scar formation after focal ischemia.Methods:Cerebral infarction model was induced by photothrombosis method.Rats were examined using MRI,and lesion volumes were estimated on day 3 post-infarction.The expression of glial fibrillary acidic protein(GFAP) and proliferating cell nuclear antigen(PCNA) was observed by immunofluorescence staining.Protein levels for GFAP,PCNA,Cyclin A and Cyclin B1 were determined by Western blot analysis from the ischemic and sham animals sacrificed at 3,7,30 days after operation.Results:Cell cycle inhibitor olomoucine significantly suppressed GFAP and PCNA expression and reduced lesion volume after cerebral ischemia.In parallel studies,we found dense astroglial scar in boundary zone of vehicle-treated rats at 7 and 30 days.Olomoucine can markedly attenuate astroglial scar formation.Western blot analysis showed increased protein levels of GFAP,PCNA,Cyclin A and Cyclin B1 after ischemia,which was reduced by olomoucine treatment.Conclusion: Our results suggested that astroglial activation,proliferation and subsequently astroglial scar formation could be partially inhibited by regulation of cell cycle.Cell cycle modulation thereby provides a potential promising strategy to treat cerebral ischemia.展开更多
Neurons and glial cells, particularly astrocytes, are the two main cell populations in the central nervous system. While it is established that brain functions primarily rely on neuronal activity, an active contributi...Neurons and glial cells, particularly astrocytes, are the two main cell populations in the central nervous system. While it is established that brain functions primarily rely on neuronal activity, an active contribution of astrocytes to information processing is only starting to be considered. There is growing evidence that astrocytes, as part of the tripartite synapse, participate in this challenge by receiving and integrating neuronal signals and, in turn, by sending signals that target neurons[1]. The involvement of astrocytes in information processing has mainly been studied at the level of the single astrocyte, often missing the role of astrocyte networks in this process.展开更多
Objective： To study the expressions of FAK and Pyk2 in human astrocytic tumors and their relationship with angiogenesis. Methods： The S-P immunohistochemical method was used to measure the expressions of FAK, Pyk2 a...Objective： To study the expressions of FAK and Pyk2 in human astrocytic tumors and their relationship with angiogenesis. Methods： The S-P immunohistochemical method was used to measure the expressions of FAK, Pyk2 and VEGF proteins in 58 human brain astrocytic tumors, and microvessel density （MVD） was detected by CD31 staining. Results： In astrocytic tumors with Ⅰ, Ⅱ, Ⅲ and Ⅳ grades, the positive rates of FAK were 20.00%, 26.67%, 44.44% and 50.00%, respectively, those of Pyk2 were 40.00%, 60.00%, 77.78% and 85.00%, respectively. FAK and Pyk2 expressions, especially Pyk2, correlated positively with VEGF expression and MVD. Conclusion： FAK and Pyk2 plays the important role in astrocytic tumor angiogenesis through regulation to VEGF.展开更多
基金Supported by Interdisziplinres Zentrum für Klinische Forschung der Universitt Würzburg,Project B25
文摘Glioblastomas are characterized by an aggressive local growth pattern, a marked degree of invasiveness and poor prognosis. Tumor invasiveness is facilitated by the increased activity of proteolytic enzymes which are involved in destruction of the extracellular matrix of the surrounding healthy brain tissue. Elevated levels of matrix metalloproteinases(MMPs) were found in glioblastoma(GBM) cell-lines, as well as in GBM biopsies as compared with low-grade astrocytoma(LGA) and normal brain samples, indicating a role in malignant progression. A careful review of the available literature revealed that both the expression and role of several of the 23 human MMP proteins is controversely discussed and for some there are no data available at all. We therefore screened a panel of 15 LGA and 15 GBM biopsy samples for those MMPs for which there is either no, very limited or even contradictory dataavailable. Hence, this is the first complete compilation of the expression pattern of all 23 human MMPs in astrocytic tumors. This study will support a better understanding of the specific expression patterns and interaction of proteolytic enzymes in malignant human glioma and may provide additional starting points for targeted patient therapy.
基金supported by the National Natural Science Foundation of China,Nos.81801220(to MGZ),81671204(to JHJ)Key Research and Development Projects of Anhui Province of China,No.202004j07020042(to JHJ)。
文摘After spinal cord injury(SCI),astrocytes gradually migrate to and surround the lesion,depositing chondroitin sulfate proteoglycan-rich extracellular matrix and forming astrocytic scar,which limits the spread of inflammation but hinders axon regeneration.Meanwhile,microglia gradually accumulate at the lesion border to form microglial scar and can polarize to generate a pro-inflammatory M1 phenotype or an anti-inflammatory M2 phenotype.However,the effect of microglia polarization on astrocytes is unclear.Here,we found that both microglia(CX3 CR1^(+))and astrocytes(GFAP^(+))gathered at the lesion border at 14 days post-injury(dpi).The microglia accumulated along the inner border of and in direct contact with the astrocytes.M1-type microglia(i NOS^(+)CX3 CR1^(+))were primarily observed at 3 and 7 dpi,while M2-type microglia(Arg1^(+)CX3 CR1^(+))were present at larger numbers at 7 and 14 dpi.Transforming growth factor-β1(TGFβ1)was highly expressed in M1 microglia in vitro,consistent with strong expression of TGFβ1 by microglia in vivo at 3 and 7 dpi,when they primarily exhibited an M1 phenotype.Furthermore,conditioned media from M1-type microglia induced astrocytes to secrete chondroitin sulfate proteoglycan in vitro.This effect was eliminated by knocking down sex-determining region Y-box 9(SOX9)in astrocytes and could not be reversed by treatment with TGFβ1.Taken together,our results suggest that microglia undergo M1 polarization and express high levels of TGFβ1 at 3 and 7 dpi,and that M1-type microglia induce astrocytes to deposit chondroitin sulfate proteoglycan via the TGFβ1/SOX9 pathway.The study was approved by the Institutional Animal Care and Use Committee of Anhui Medical University,China(approval No.LLSC20160052)on March 1,2016.
基金financially supported by the National Natural Science Foundation of China,No.81303115,81774042 (both to XC)the Pearl River S&T Nova Program of Guangzhou,No.201806010025 (to XC)+3 种基金the Specialty Program of Guangdong Province Hospital of Chinese Medicine of China,No.YN2018ZD07 (to XC)the Natural Science Foundatior of Guangdong Province of China,No.2023A1515012174 (to JL)the Science and Technology Program of Guangzhou of China,No.20210201 0268 (to XC),20210201 0339 (to JS)Guangdong Provincial Key Laboratory of Research on Emergency in TCM,Nos.2018-75,2019-140 (to JS)
文摘Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.
基金supported in part by a Grant from AMED(17ek0109120h0003)a Grant-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology(17K08324 and 15H04892)
文摘Astrocytic Kir4.1 channels and spatial potassium buffering：Astrocytes play a crucial role in maintaining the structural and functional integrity of the brain,which includes formation of the blood-brain barrier,maintenance of water and ion homeostasis,metabolism of neurotransmitters and secretion of various neuroactive molecules.
文摘Background Our previous study confirmed that oligodendrogliomas had higher frequency of chromosome 1p/19q deletion. In order to improve the diagnostic criteria and to predict the prognosis of oligodendroglioma patients, the status of chromosome 1 p/19q deletion, the methylation of O6-methylguanine-DNA methyltransferase （MGMT）, and the expression of p53 protein were evaluated and investigated in relation to patients＇ outcomes.Methods Methylation of MGMT in 73 cases was analyzed by nested methylation-specific PCR （MSP）. The levels of MGMT and p53 protein were tested with immunohistochemistry. Pearson＇s chi-square test and Fisher＇s exact test were used. Multivariate and Kaplan-Meier analysis were performed to determine patients＇ outcomes.Results Both oligodendrogliomas and astrocytic gliomas exhibited frequent methylation of MGMT. However, the results of MSP did not completely correspond to that of the immunohistochemical staining for MGMT. The expression of p53 protein was more frequently observed in patients without a 1 p or 19q deletion in anaplastic oligodendrogliomas （=0.032,0.025）. In low-grade oligodendrogliomas, methylation of MGMT was more frequent in patients with 1 p/19q deletion than in patients with 1p/19q intact （P=0.038）. Patients with oligodendrogliomas with 1p/19q loss of heterozygosity and p53-negative showed a longer progression-free survival.Conclusion Detection of chromosome 1p/19q status combined with p53 protein immunohistochemistry might be beneficial to improve the pathological diagnosis and to determine the prognosis of patients with oligodendrogliomas.
基金a grant from Doctor Point Foundation of Ministry of Education of China (No. 2004 0487060)
文摘To explore the roles of astrocytes in the epileptogenesis, astrocytes and neurons were isolated, purified and cultured in vitro from cerebral cortex of rats. The astrocytes were activated by ciliary neurotrophic factor (CNTF) and astrocytic conditioned medium (ACM) was collected to treat neurons for 4, 8 and 12 h. By using Western blot, the expression of calmodulin dependent protein kinase Ⅱ (CaMKⅡ), inducible nitric oxide synthase (iNOS) and adenylate cyclase (AC) was de- tected in neurons. The results showed that the expression of CaMKⅡ, iNOS and AC was increased significantly in the neurons treated with ACM from 4 h to 12 h (P<0.05), and that of iNOS and AC peaked at 8 h and 12 h respectively. It was suggested that there might be some epileptogenic factors in the ACM and such signal pathways as NOS-NO-cGMP, Ca2+?CaM-CaMKⅡ and AC-cAMP-PKA might take part in the signal transduction of epileptogenesis.
文摘Dynamic structuring and functions of perisynaptic astrocytic processes and of the gap junction network within a single astrocyte are outlined. Motile perisynaptic astrocytic processes are generating microdomains. By contacting and retracting of their endfeet an appropriate receptor pattern is selected that modulates the astrocytic receptor sheath for its activation by neurotransmitter substances, ions, transporters, etc. This synaptic information processing occurs in three distinct time scales of milliseconds to seconds, seconds to minutes, hours or longer. Simultaneously, the interconnecting gap junctions are activated by building a network within the astrocyte. Frequently activated gap junction cycles become embodied in gap junction plaques. The gap junction network formation and gap junction plaques are governed and controlled in the same time scales as synaptic information processing. Biomimetic computer systems may represent an alternative to limitations of brainphysiological research. The model proposed allows the interpretation of affective psychoses and schizophrenia as time disorders basically determined by a shortened, prolonged or lacking time scale of synaptic information processing.
文摘In chronic schizophrenia, synaptic information processing is unbalanced, as shown in a model of glial-neuronal synaptic units, called tripartite synapses. The glial component of the synapse exerts a modifying function in neurotransmission since the astrocyte activated by neurotransmitters produces gliotransmitters that negatively feedback to the presynapse. It is hypothesized that in schizophrenia nonfunctional astrocytic receptors cannot be activated, thus losing their modulating function. This causes a generalization of information processing in the neuronal networks such that the brain is unable to distinguish between subjects and objects in the environment. Delusions, hallucinations and cognitive impairment occur on the behavioral level. In a model of a cholinergic tripartite synapse, it is shown that glial binding proteins modify neurotransmission by occupancy with cognate neurotransmitters temporarily turning off neurotransmission on the presynapse. Most recently, glial binding proteins have been engineered. It is proposed that the substitution of glial binding proteins may balance synaptic information processing in schizophrenia since these proteins exert a modulatory function comparable to functional astrocytic receptors. Rap- id technical developments may enable this novel treatment approach in schizophrenia.
基金This study was supported by a grant from the National Nature Science Foundation of China(No.30230140,30400142)
文摘Background:Astrocytes become reactive following many types of CNS injuries.Excessive astrogliosis is detrimental and contributes to neuronal damage.We sought to determine whether inhibition of cell cycle could decrease the proliferation of astroglial cells and therefore reduce excessive gliosis and glial scar formation after focal ischemia.Methods:Cerebral infarction model was induced by photothrombosis method.Rats were examined using MRI,and lesion volumes were estimated on day 3 post-infarction.The expression of glial fibrillary acidic protein(GFAP) and proliferating cell nuclear antigen(PCNA) was observed by immunofluorescence staining.Protein levels for GFAP,PCNA,Cyclin A and Cyclin B1 were determined by Western blot analysis from the ischemic and sham animals sacrificed at 3,7,30 days after operation.Results:Cell cycle inhibitor olomoucine significantly suppressed GFAP and PCNA expression and reduced lesion volume after cerebral ischemia.In parallel studies,we found dense astroglial scar in boundary zone of vehicle-treated rats at 7 and 30 days.Olomoucine can markedly attenuate astroglial scar formation.Western blot analysis showed increased protein levels of GFAP,PCNA,Cyclin A and Cyclin B1 after ischemia,which was reduced by olomoucine treatment.Conclusion: Our results suggested that astroglial activation,proliferation and subsequently astroglial scar formation could be partially inhibited by regulation of cell cycle.Cell cycle modulation thereby provides a potential promising strategy to treat cerebral ischemia.
文摘Neurons and glial cells, particularly astrocytes, are the two main cell populations in the central nervous system. While it is established that brain functions primarily rely on neuronal activity, an active contribution of astrocytes to information processing is only starting to be considered. There is growing evidence that astrocytes, as part of the tripartite synapse, participate in this challenge by receiving and integrating neuronal signals and, in turn, by sending signals that target neurons[1]. The involvement of astrocytes in information processing has mainly been studied at the level of the single astrocyte, often missing the role of astrocyte networks in this process.
基金the Science Research Foundation of Health Department of Hubei Province (No. JX1B019)the Science Research Foundation of Wuahn University (No. 301270064)
文摘Objective： To study the expressions of FAK and Pyk2 in human astrocytic tumors and their relationship with angiogenesis. Methods： The S-P immunohistochemical method was used to measure the expressions of FAK, Pyk2 and VEGF proteins in 58 human brain astrocytic tumors, and microvessel density （MVD） was detected by CD31 staining. Results： In astrocytic tumors with Ⅰ, Ⅱ, Ⅲ and Ⅳ grades, the positive rates of FAK were 20.00%, 26.67%, 44.44% and 50.00%, respectively, those of Pyk2 were 40.00%, 60.00%, 77.78% and 85.00%, respectively. FAK and Pyk2 expressions, especially Pyk2, correlated positively with VEGF expression and MVD. Conclusion： FAK and Pyk2 plays the important role in astrocytic tumor angiogenesis through regulation to VEGF.
