Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia,but the underlying mechanism has not yet been fully elucidated.Studies have shown that autophagy plays an important role in...Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia,but the underlying mechanism has not yet been fully elucidated.Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment,and the phosphoinositide 3-kinase(PI3K)/Akt signaling pathway plays an important role in autophagy regulation.To investigate the role played by the PI3K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models,we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method.Starting at 2 hours after modeling,electroacupuncture was delivered at the Shenting(GV24)and Baihui(GV20)acupoints,with a dilatational wave(1-20 Hz frequency,2 mA intensity,6 V peak voltage),for 30 minutes/day over 8 consecutive days.Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury,increased the mRNA expression levels of the PI3K/Akt signaling pathwayrelated factors Beclin-1,mammalian target of rapamycin(mTOR),and PI3K,increased the protein expression levels of phosphorylated Akt,Beclin-1,PI3K,and mTOR in the ischemic cerebral cortex,and simultaneously reduced p53 mRNA and protein expression levels.In the Morris water maze test,the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.In the spatial probe test,the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.Electroacupuncture stimulation applied to the Shenting(GV24)and Baihui(GV20)acupoints activated the PI3K/Akt signaling pathway and improved rat learning and memory impairment.This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan Unive展开更多
Objective: To analyze the dynamic change of serum protein S100b in patients with traumatic brain injury and its clinical value in assessing brain damage. Methods: According to Glasgow coma scale (GCS), 102 cases of tr...Objective: To analyze the dynamic change of serum protein S100b in patients with traumatic brain injury and its clinical value in assessing brain damage. Methods: According to Glasgow coma scale (GCS), 102 cases of traumatic brain injury were divided into mild brain injury group (GCS≥13, n=31, Group A), moderate brain injury group (8<GCS<13, n=37, Group B) and severe brain injury group (GCS≤8, n=34, Group C). Serial S100b concentrations were analyzed by enzyme-linked immunosorbent assay (ELISA) in blood samples taken on admission, 12 h, 24 h, 48 h, 72 h and 7 days after traumatic brain injury. Results: The severe brain injury group showed significantly higher concentration of serum S100b, with earlier increase and longer duration, than the mild and moderate brain injury groups. The patients with higher S100b exhibited lower GCS scores and poor clinical prognosis. The increase in S100b could emerge before clinical image evidence indicated so. Conclusions: Serum S100b can be used as a sensitive index for assessment and prediction of traumatic brain injury severity and prognosis.展开更多
Large bone defects resulting from fractures and disease are a major clinical challenge,being often unable to heal spontaneously by the body’s repair mechanisms.Lines of evidence have shown that hypoxia-induced overpr...Large bone defects resulting from fractures and disease are a major clinical challenge,being often unable to heal spontaneously by the body’s repair mechanisms.Lines of evidence have shown that hypoxia-induced overproduction of ROS in bone defect region has a major impact on delaying bone regeneration.However,replenishing excess oxygen in a short time cause high oxygen tension that affect the activity of osteoblast precursor cells.Therefore,reasonably restoring the hypoxic condition of bone microenvironment is essential for facilitating bone repair.Herein,we designed ROS scavenging and responsive prolonged oxygen-generating hydrogels(CPP-L/GelMA)as a“bone microenvironment regulative hydrogel”to reverse the hypoxic microenvironment in bone defects region.CPP-L/GelMA hydrogels comprises an antioxidant enzyme catalase(CAT)and ROS-responsive oxygen-releasing nanoparticles(PFC@PLGA/PPS)co-loaded liposome(CCP-L)and GelMA hydrogels.Under hypoxic condition,CPP-L/GelMA can release CAT for degrading hydrogen peroxide to generate oxygen and be triggered by superfluous ROS to continuously release the oxygen for more than 2 weeks.The prolonged oxygen enriched microenvironment generated by CPP-L/GelMA hydrogel significantly enhanced angiogenesis and osteogenesis while inhibited osteoclastogenesis.Finally,CPP-L/GelMA showed excellent bone regeneration effect in a mice skull defect model through the Nrf2-BMAL1-autophagy pathway.Hence,CPP-L/GelMA,as a bone microenvironment regulative hydrogel for bone tissue respiration,can effectively scavenge ROS and provide prolonged oxygen supply according to the demand in bone defect region,possessing of great clinical therapeutic potential.展开更多
目的研究高频重复经颅磁刺激(rTMS)对全脑缺血大鼠学习记忆的影响并探讨其机制。方法将体重210~250g的35只雄性SD大鼠(8~10周龄)按随机区组法随机分为假手术组(8只)、模型组(9只)、rTMS组(9只)、假刺激组(9只),采用改良四血管阻断法制...目的研究高频重复经颅磁刺激(rTMS)对全脑缺血大鼠学习记忆的影响并探讨其机制。方法将体重210~250g的35只雄性SD大鼠(8~10周龄)按随机区组法随机分为假手术组(8只)、模型组(9只)、rTMS组(9只)、假刺激组(9只),采用改良四血管阻断法制作全脑缺血大鼠模型,其中rTMS组给予连续2周的10HzrTMS刺激,假刺激组给予假刺激。利用Morris水迷宫检测大鼠空间学习记忆能力,多通道在体记录技术采集海马CA1区局部场电位(local field potentials,LFPs)分析θ和γ节律振荡,免疫组织化学和蛋白免疫印迹法检测海马组织蛋白激酶A(PKA)、磷酸化环磷腺苷效应元件结合蛋白(p-CREB)表达。结果模型组与假手术组相比,平均逃避潜伏期延长[(35.16±0.80)s与(16.57±0.74)s,k=3.723,P=0.013]、跨越平台次数减少[(1.14±0.42)次与(4.46±0.23)次,k=3.185,P=0.042]以及原平台象限游泳时间缩短[(14.46±0.73)s与(29.31±0.42)s,k=3.027,P=0.047],海马CA1区LFPsθ和γ功率谱密度均值降低[分别为(-68.48±2.61)Hz与(-59.38±2.25)Hz,k=2.958,P=0.048;(-82.23±4.60)Hz与(-70.50±4.25)Hz,k=3.729,P=0.021],免疫组织化学染色显示海马PKA、p-CREB表达减少(分别为7184.26±975.12与25137.35±1010.62,k=3.588,P=0.027;1803.73±336.18与20175.25±727.23,k=2.912,P=0.049);rTMS组与模型组相比,平均逃避潜伏期缩短[(24.69±1.01)s与(35.16±0.80)s,k=4.082,P=0.034]、跨越平台次数增加[(2.42±0.31)次与(1.14±0.42)次,t=3.296,P=0.039]及原平台象限游泳时间延长[(23.07±0.67)s与(14.46±0.73)s,k=4.323,P=0.012],海马CA1区LFPsθ和γ功率谱密度均值升高[分别为(-63.81±3.12)Hz与(-68.48±2.61)Hz,k=3.582,P=0.015;(-75.80±4.58)Hz与(-82.23±4.60)Hz,k=4.051,P=0.026],免疫组织化学染色显示海马PKA、p-CREB表达增加(分别为13065.32±1045.18与7184.26±975.12,k=3.923,P=0.031;11032.83±562.86与1803.73±336.18,k=3.178,P=0.038)。结论高频rTMS可能通过增强海马CA1区θ和γ振荡和提高海马PKA、p-CREB蛋白表达,展开更多
Atorvastatin has been shown to be a safe and effective non-surgical treatment option for patients with chronic subdural hematoma.However,treatment with atorvastatin is not effective in some patients,who must undergo f...Atorvastatin has been shown to be a safe and effective non-surgical treatment option for patients with chronic subdural hematoma.However,treatment with atorvastatin is not effective in some patients,who must undergo further surgical treatment.Dexamethasone has anti-inflammatory and immunomodulatory effects,and low dosages are safe and effective for the treatment of many diseases,such as ankylosing spondylitis and community-acquired pneumonia.However,the effects of atorvastatin and low-dose dexamethasone for the treatment of chronic subdural hematoma remain poorly understood.Hematoma samples of patients with chronic subdural hematoma admitted to the General Hospital of Tianjin Medical University of China were collected and diluted in endothelial cell medium at 1:1 as the hematoma group.Atorvastatin,dexamethasone,or their combination was added to the culture medium.The main results were as follows:hopping probe ion conductance microscopy and permeability detection revealed that the best dosages to improve endothelial cell permeability were 0.1μM atorvastatin and 0.1μM dexamethasone.Atorvastatin,dexamethasone,or their combination could markedly improve the recovery of injured endothelial cells.Mice subcutaneously injected with diluted hematoma solution and then treated with atorvastatin,dexamethasone,or their combination exhibited varying levels of rescue of endothelial cell function.Hopping probe ion conductance microscopy,western blot assay,and polymerase chain reaction to evaluate the status of human cerebral endothelial cell status and expression level of tight junction protein indicated that atorvastatin,dexamethasone,or their combination could reduce subcutaneous vascular leakage caused by hematoma fluid.Moreover,the curative effect of the combined treatment was significantly better than that of either single treatment.Expression of Krüppel-like factor 2 protein in human cerebral endothelial cells was significantly increased,as was expression of the tight junction protein and vascular permeability marker va展开更多
Objective： To determine the changes of serum Tau protein, glial fibrillary acidic protein （GFAP）, tumor necrosis factor alpha （TNF-α）, and malonaldehyde （MDA） in rats after blast-related traumatic brain injury...Objective： To determine the changes of serum Tau protein, glial fibrillary acidic protein （GFAP）, tumor necrosis factor alpha （TNF-α）, and malonaldehyde （MDA） in rats after blast-related traumatic brain injury （BTBI） and to provide relative information for further studies on BTBI mechanism and seek specific biomarkers for BTBI. Methods： Ninety male Sprague-Dawley rats were randomly assigned into three groups： control group, moderate blast injury group, and severe blast injury group （n=30 for each）. Rats in the moderate and severe blast injury groups were respectively exposed to corresponding levels of BTBI. After explosion, serum levels of Tau, GFAP, TNF-α, and MDA in each group were determined by Elisa assay at different time points after injury （8 h, 24 h, 3 d, and 6 d）. The extent of brain damage was detected by Nissl staining and TUNEL assay. Results： Serum levels of Tau and GFAP rapidly increased and reached the peak at 24 h after either moderate or severe blast injury. All the values were significantly higher than control group at all time points （P〈0.05）. Serum TNF-α level of both injury groups peaked at 8 h after BTBI and stayed significantly higher than control group at all time points （P〈0.05）. Serum MDA of two injury groups began to significantly increase at 3 d and the level stayed significantly higher than control group until 6 d （P〈0.05）. Moreover, unlike the other biomarkers, serum MDA of severe blast injury group was significantly higher than moderate blast injury group at 6 d （P〈0.05）. Conclusion： The changes of serum Tau, GFAP, and TNF-α showed a good sensitivity at the acute phase after BTBI （within 24 h）. However, their specificity and correlation with the extent of injury were limited in this experiment. Moreover, although the change of serum MDA showed a poor sensitivity and specificity to the diagnosis of BTBI during the first few days, it can reflect the injury degree at 6 d after injury. Therefore, further studies are nee展开更多
Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signalin...Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.展开更多
Background:Traumatic brain edema(TBE)is caused by a specific water channel mediated by membrane aquaporins.Aquaporin-4(AQP4)plays an especially important role in this process,but the relationship between AQP4 and TBE ...Background:Traumatic brain edema(TBE)is caused by a specific water channel mediated by membrane aquaporins.Aquaporin-4(AQP4)plays an especially important role in this process,but the relationship between AQP4 and TBE remains unclear.The purpose of this study was to explore expression of AQP4 in the hippocampus after traumatic brain injury(TBI),as well as the effect of brain edema on skeletal protein and its function in hippocampal neurons.Methods:The adult male Wistar rats we divided into a sham group and a TBI group,the latter of which was further divided into 1,3,6,12,24 and 72 hours(h)and 15 days(d)post injury subgroups.A proper TBI model was established,and brain edema was assessed in each group by water content.We measured the abundance of various proteins,including hypoxia inducible factor-1α(HIF-1α),AQP4,microtubule-associated protein 2(MAP2),tau-5 protein,phosphorylated level of TAU,synaptophysin,cyclic adenosine monophosphate response element binding protein(CREB),phosphorylated CREB and general control nonrepressed 2,in each group.Hippocampal neurons and spatial memory test were analyzed in different time points.Results:Compared with that in the sham group,the level of AQP4 in hippocampal neurons began to significantly increase at 1 h post TBI and then decreased at 15 d post TBI.During this time frame,AQP4 level peaked at 12 and 72 h,and these peaks were closely correlated with high brain water content.HIF-1αdisplayed a similar trend.Conversely,levels of MAP2 began to decrease at 1 h post TBI and then increase at 15 d post TBI.In addition,the most severe brain edema in rats was found at 24 h post TBI,with neuronal loss and hippocampal dendritic spine injury.Compared to those in the sham group,rats in the TBI groups had significantly prolonged latency and significantly shortened exploration time.Conclusions:AQP4 level was closely correlated with severity of brain edema,and abnormal levels thereof aggravated such severity after TBI.展开更多
基金supported by the National Natural Science Foundation of China,No.81574042the Traditional Chinese Medicine Special Research Projects of Henan Province of China,No.2018JDZX011(both to XDF).
文摘Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia,but the underlying mechanism has not yet been fully elucidated.Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment,and the phosphoinositide 3-kinase(PI3K)/Akt signaling pathway plays an important role in autophagy regulation.To investigate the role played by the PI3K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models,we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method.Starting at 2 hours after modeling,electroacupuncture was delivered at the Shenting(GV24)and Baihui(GV20)acupoints,with a dilatational wave(1-20 Hz frequency,2 mA intensity,6 V peak voltage),for 30 minutes/day over 8 consecutive days.Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury,increased the mRNA expression levels of the PI3K/Akt signaling pathwayrelated factors Beclin-1,mammalian target of rapamycin(mTOR),and PI3K,increased the protein expression levels of phosphorylated Akt,Beclin-1,PI3K,and mTOR in the ischemic cerebral cortex,and simultaneously reduced p53 mRNA and protein expression levels.In the Morris water maze test,the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.In the spatial probe test,the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.Electroacupuncture stimulation applied to the Shenting(GV24)and Baihui(GV20)acupoints activated the PI3K/Akt signaling pathway and improved rat learning and memory impairment.This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan Unive
文摘Objective: To analyze the dynamic change of serum protein S100b in patients with traumatic brain injury and its clinical value in assessing brain damage. Methods: According to Glasgow coma scale (GCS), 102 cases of traumatic brain injury were divided into mild brain injury group (GCS≥13, n=31, Group A), moderate brain injury group (8<GCS<13, n=37, Group B) and severe brain injury group (GCS≤8, n=34, Group C). Serial S100b concentrations were analyzed by enzyme-linked immunosorbent assay (ELISA) in blood samples taken on admission, 12 h, 24 h, 48 h, 72 h and 7 days after traumatic brain injury. Results: The severe brain injury group showed significantly higher concentration of serum S100b, with earlier increase and longer duration, than the mild and moderate brain injury groups. The patients with higher S100b exhibited lower GCS scores and poor clinical prognosis. The increase in S100b could emerge before clinical image evidence indicated so. Conclusions: Serum S100b can be used as a sensitive index for assessment and prediction of traumatic brain injury severity and prognosis.
基金supported by National Science Foundation of China(Grant No.32271409,82002370,31800806)National Basic Research Program of China(2021YFA1201404)+5 种基金China Postdoctoral Science Foundation(Grant No.2019M661806)Major Project of NSFC(81991514)Natural Science Foundation of Jiangsu Province(Grant No.BK20200117)Jiangsu postdoctoral research support project(Grant No.2021K059A)Program of Innovation and Entrepreneurship of Jiangsu Province,Jiangsu Provincial Key Medical Center Foundation,Jiangsu Provincial Medical Outstanding Talent Foundation,Jiangsu Provincial Medical Youth Talent Foundation and Jiangsu Provincial Key Medical Talent Foundation,the Fundamental Research Funds for the Central Universities(14380493,14380494)Changzhou Sci&Tech Program(Grant No.CJ20220103).
文摘Large bone defects resulting from fractures and disease are a major clinical challenge,being often unable to heal spontaneously by the body’s repair mechanisms.Lines of evidence have shown that hypoxia-induced overproduction of ROS in bone defect region has a major impact on delaying bone regeneration.However,replenishing excess oxygen in a short time cause high oxygen tension that affect the activity of osteoblast precursor cells.Therefore,reasonably restoring the hypoxic condition of bone microenvironment is essential for facilitating bone repair.Herein,we designed ROS scavenging and responsive prolonged oxygen-generating hydrogels(CPP-L/GelMA)as a“bone microenvironment regulative hydrogel”to reverse the hypoxic microenvironment in bone defects region.CPP-L/GelMA hydrogels comprises an antioxidant enzyme catalase(CAT)and ROS-responsive oxygen-releasing nanoparticles(PFC@PLGA/PPS)co-loaded liposome(CCP-L)and GelMA hydrogels.Under hypoxic condition,CPP-L/GelMA can release CAT for degrading hydrogen peroxide to generate oxygen and be triggered by superfluous ROS to continuously release the oxygen for more than 2 weeks.The prolonged oxygen enriched microenvironment generated by CPP-L/GelMA hydrogel significantly enhanced angiogenesis and osteogenesis while inhibited osteoclastogenesis.Finally,CPP-L/GelMA showed excellent bone regeneration effect in a mice skull defect model through the Nrf2-BMAL1-autophagy pathway.Hence,CPP-L/GelMA,as a bone microenvironment regulative hydrogel for bone tissue respiration,can effectively scavenge ROS and provide prolonged oxygen supply according to the demand in bone defect region,possessing of great clinical therapeutic potential.
文摘目的研究高频重复经颅磁刺激(rTMS)对全脑缺血大鼠学习记忆的影响并探讨其机制。方法将体重210~250g的35只雄性SD大鼠(8~10周龄)按随机区组法随机分为假手术组(8只)、模型组(9只)、rTMS组(9只)、假刺激组(9只),采用改良四血管阻断法制作全脑缺血大鼠模型,其中rTMS组给予连续2周的10HzrTMS刺激,假刺激组给予假刺激。利用Morris水迷宫检测大鼠空间学习记忆能力,多通道在体记录技术采集海马CA1区局部场电位(local field potentials,LFPs)分析θ和γ节律振荡,免疫组织化学和蛋白免疫印迹法检测海马组织蛋白激酶A(PKA)、磷酸化环磷腺苷效应元件结合蛋白(p-CREB)表达。结果模型组与假手术组相比,平均逃避潜伏期延长[(35.16±0.80)s与(16.57±0.74)s,k=3.723,P=0.013]、跨越平台次数减少[(1.14±0.42)次与(4.46±0.23)次,k=3.185,P=0.042]以及原平台象限游泳时间缩短[(14.46±0.73)s与(29.31±0.42)s,k=3.027,P=0.047],海马CA1区LFPsθ和γ功率谱密度均值降低[分别为(-68.48±2.61)Hz与(-59.38±2.25)Hz,k=2.958,P=0.048;(-82.23±4.60)Hz与(-70.50±4.25)Hz,k=3.729,P=0.021],免疫组织化学染色显示海马PKA、p-CREB表达减少(分别为7184.26±975.12与25137.35±1010.62,k=3.588,P=0.027;1803.73±336.18与20175.25±727.23,k=2.912,P=0.049);rTMS组与模型组相比,平均逃避潜伏期缩短[(24.69±1.01)s与(35.16±0.80)s,k=4.082,P=0.034]、跨越平台次数增加[(2.42±0.31)次与(1.14±0.42)次,t=3.296,P=0.039]及原平台象限游泳时间延长[(23.07±0.67)s与(14.46±0.73)s,k=4.323,P=0.012],海马CA1区LFPsθ和γ功率谱密度均值升高[分别为(-63.81±3.12)Hz与(-68.48±2.61)Hz,k=3.582,P=0.015;(-75.80±4.58)Hz与(-82.23±4.60)Hz,k=4.051,P=0.026],免疫组织化学染色显示海马PKA、p-CREB表达增加(分别为13065.32±1045.18与7184.26±975.12,k=3.923,P=0.031;11032.83±562.86与1803.73±336.18,k=3.178,P=0.038)。结论高频rTMS可能通过增强海马CA1区θ和γ振荡和提高海马PKA、p-CREB蛋白表达,
基金supported by the National Natural Science Foundation of China,Nos.81671380(to DW),81720108015(to JNZ),81930031(to JNZ),81771221(to YL),and 81901525(to SZ)the Clinical Study of Tianjin Medical University of China,No.2017kylc007(to RCJ)+1 种基金the Natural Science Foundation of Tianjin of China,No.17JCZDJC35900(to DW)the Tianjin Science and Technology Plan Program of China,No.19YFZCSY00650(to RCJ)。
文摘Atorvastatin has been shown to be a safe and effective non-surgical treatment option for patients with chronic subdural hematoma.However,treatment with atorvastatin is not effective in some patients,who must undergo further surgical treatment.Dexamethasone has anti-inflammatory and immunomodulatory effects,and low dosages are safe and effective for the treatment of many diseases,such as ankylosing spondylitis and community-acquired pneumonia.However,the effects of atorvastatin and low-dose dexamethasone for the treatment of chronic subdural hematoma remain poorly understood.Hematoma samples of patients with chronic subdural hematoma admitted to the General Hospital of Tianjin Medical University of China were collected and diluted in endothelial cell medium at 1:1 as the hematoma group.Atorvastatin,dexamethasone,or their combination was added to the culture medium.The main results were as follows:hopping probe ion conductance microscopy and permeability detection revealed that the best dosages to improve endothelial cell permeability were 0.1μM atorvastatin and 0.1μM dexamethasone.Atorvastatin,dexamethasone,or their combination could markedly improve the recovery of injured endothelial cells.Mice subcutaneously injected with diluted hematoma solution and then treated with atorvastatin,dexamethasone,or their combination exhibited varying levels of rescue of endothelial cell function.Hopping probe ion conductance microscopy,western blot assay,and polymerase chain reaction to evaluate the status of human cerebral endothelial cell status and expression level of tight junction protein indicated that atorvastatin,dexamethasone,or their combination could reduce subcutaneous vascular leakage caused by hematoma fluid.Moreover,the curative effect of the combined treatment was significantly better than that of either single treatment.Expression of Krüppel-like factor 2 protein in human cerebral endothelial cells was significantly increased,as was expression of the tight junction protein and vascular permeability marker va
基金The work was supported by National Natural Science Foundation of China （No. 30930093）, National Science and Technology Major Project of China （2013ZX 09J13109-02C）, National Science ＆ Technology Pillar Program of China （No. 2012BAI11B02）, Program for Changjiang Scholars and Innovative Research Team in University （No. IRT1053）, and Research Foundation of PLA （No. 2010gxjs078 and No. AWS11J008）.
文摘Objective： To determine the changes of serum Tau protein, glial fibrillary acidic protein （GFAP）, tumor necrosis factor alpha （TNF-α）, and malonaldehyde （MDA） in rats after blast-related traumatic brain injury （BTBI） and to provide relative information for further studies on BTBI mechanism and seek specific biomarkers for BTBI. Methods： Ninety male Sprague-Dawley rats were randomly assigned into three groups： control group, moderate blast injury group, and severe blast injury group （n=30 for each）. Rats in the moderate and severe blast injury groups were respectively exposed to corresponding levels of BTBI. After explosion, serum levels of Tau, GFAP, TNF-α, and MDA in each group were determined by Elisa assay at different time points after injury （8 h, 24 h, 3 d, and 6 d）. The extent of brain damage was detected by Nissl staining and TUNEL assay. Results： Serum levels of Tau and GFAP rapidly increased and reached the peak at 24 h after either moderate or severe blast injury. All the values were significantly higher than control group at all time points （P〈0.05）. Serum TNF-α level of both injury groups peaked at 8 h after BTBI and stayed significantly higher than control group at all time points （P〈0.05）. Serum MDA of two injury groups began to significantly increase at 3 d and the level stayed significantly higher than control group until 6 d （P〈0.05）. Moreover, unlike the other biomarkers, serum MDA of severe blast injury group was significantly higher than moderate blast injury group at 6 d （P〈0.05）. Conclusion： The changes of serum Tau, GFAP, and TNF-α showed a good sensitivity at the acute phase after BTBI （within 24 h）. However, their specificity and correlation with the extent of injury were limited in this experiment. Moreover, although the change of serum MDA showed a poor sensitivity and specificity to the diagnosis of BTBI during the first few days, it can reflect the injury degree at 6 d after injury. Therefore, further studies are nee
基金supported by the National Natural Science Foundation of China,Nos.82230042 and 81930029(to ZY),U2004201(to FG and RYP)the China Postdoctoral Science Foundation,No.2020M683748(to RYP)。
文摘Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.
文摘Background:Traumatic brain edema(TBE)is caused by a specific water channel mediated by membrane aquaporins.Aquaporin-4(AQP4)plays an especially important role in this process,but the relationship between AQP4 and TBE remains unclear.The purpose of this study was to explore expression of AQP4 in the hippocampus after traumatic brain injury(TBI),as well as the effect of brain edema on skeletal protein and its function in hippocampal neurons.Methods:The adult male Wistar rats we divided into a sham group and a TBI group,the latter of which was further divided into 1,3,6,12,24 and 72 hours(h)and 15 days(d)post injury subgroups.A proper TBI model was established,and brain edema was assessed in each group by water content.We measured the abundance of various proteins,including hypoxia inducible factor-1α(HIF-1α),AQP4,microtubule-associated protein 2(MAP2),tau-5 protein,phosphorylated level of TAU,synaptophysin,cyclic adenosine monophosphate response element binding protein(CREB),phosphorylated CREB and general control nonrepressed 2,in each group.Hippocampal neurons and spatial memory test were analyzed in different time points.Results:Compared with that in the sham group,the level of AQP4 in hippocampal neurons began to significantly increase at 1 h post TBI and then decreased at 15 d post TBI.During this time frame,AQP4 level peaked at 12 and 72 h,and these peaks were closely correlated with high brain water content.HIF-1αdisplayed a similar trend.Conversely,levels of MAP2 began to decrease at 1 h post TBI and then increase at 15 d post TBI.In addition,the most severe brain edema in rats was found at 24 h post TBI,with neuronal loss and hippocampal dendritic spine injury.Compared to those in the sham group,rats in the TBI groups had significantly prolonged latency and significantly shortened exploration time.Conclusions:AQP4 level was closely correlated with severity of brain edema,and abnormal levels thereof aggravated such severity after TBI.
