Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-i...Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.展开更多
Due to its high incidence, high disability rate, and high mortality rate, traumatic brain injury （TBI） poses a serious threat to human health. This manuscript describes the urgent problems currently existing in Chin...Due to its high incidence, high disability rate, and high mortality rate, traumatic brain injury （TBI） poses a serious threat to human health. This manuscript describes the urgent problems currently existing in China＇s TBI treatment and proposes a scheme of a nationwide collaboration platform for the treatment of TBI so as to improve the overall level of TBl treatment in China, and reduce disability and mortality rates in TBI patients.展开更多
Background: Decompressive craniectomy (DC) has been the classical management for malignant middle cerebral artery infarctions (mMCAI) in clinical practice. However, the association between DC and mMCAI remains unclear...Background: Decompressive craniectomy (DC) has been the classical management for malignant middle cerebral artery infarctions (mMCAI) in clinical practice. However, the association between DC and mMCAI remains unclear. This review went to evaluate the efficacy of DC in treating mMCAI patients. Methods: Studies were entirely searched since the foundation dates of multiple databases to June 2016. All major databases were involved, including Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, and other sources. the bias risk of studies involved were evaluated. Modified Rankin Scale was defined as Primary outcome, Odds Ratio and 95% confidence intervals was taken as measurements. T2 (tau-squared) test, I2 test, and chi-square tests were used for statistical heterogeneity evaluation for each meta-analysis result, followed by fixed-effect model. Mantel-haenszel method was used in the process of summary estimations. All of the meta-analysis was conducted by Review Manager 5.3.Results & Conclusion: One thousand one hundred forty-five records of data were critically identified and collected through databases and 14 studies were finally involved. Result suggested that DC can ameliorate the suboptimal outcome of mMCAI patients.展开更多
基金supported by research grants from the Ningbo Science and Technology Plan Project,No.2022Z143hezuo(to BL)the National Natural Science Foundation of China,No.82201520(to XD)。
文摘Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.
基金This work was supported by the research grants from the National Natural Science Foundation of China （No. 81171144, No. 81471238）.
文摘Due to its high incidence, high disability rate, and high mortality rate, traumatic brain injury （TBI） poses a serious threat to human health. This manuscript describes the urgent problems currently existing in China＇s TBI treatment and proposes a scheme of a nationwide collaboration platform for the treatment of TBI so as to improve the overall level of TBl treatment in China, and reduce disability and mortality rates in TBI patients.
文摘Background: Decompressive craniectomy (DC) has been the classical management for malignant middle cerebral artery infarctions (mMCAI) in clinical practice. However, the association between DC and mMCAI remains unclear. This review went to evaluate the efficacy of DC in treating mMCAI patients. Methods: Studies were entirely searched since the foundation dates of multiple databases to June 2016. All major databases were involved, including Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, and other sources. the bias risk of studies involved were evaluated. Modified Rankin Scale was defined as Primary outcome, Odds Ratio and 95% confidence intervals was taken as measurements. T2 (tau-squared) test, I2 test, and chi-square tests were used for statistical heterogeneity evaluation for each meta-analysis result, followed by fixed-effect model. Mantel-haenszel method was used in the process of summary estimations. All of the meta-analysis was conducted by Review Manager 5.3.Results & Conclusion: One thousand one hundred forty-five records of data were critically identified and collected through databases and 14 studies were finally involved. Result suggested that DC can ameliorate the suboptimal outcome of mMCAI patients.
