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Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke
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作者 Julia Castillo-González Elena González-Rey 《Neural Regeneration Research》 SCIE CAS 2025年第7期1944-1956,共13页
The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting... The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases. 展开更多
关键词 bloodbrain barrier disruption drug delivery ischemic stroke NEUROINFLAMMATION tight-junctions
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Inhibition of chemokine-like factor 1 improves bloodbrain barrier dysfunction in rats following focal cerebral ischemia 被引量:10
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作者 KONG Ling-lei HU Jin-feng +2 位作者 YUAN Yu-he CHEN Nai-hong DU Guan-hua 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2016年第10期1024-1025,共2页
OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was ... OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was applied to the rightcerebral ventricle immediately after transient middle cerebral artery occlusion.Brain water content,Evans blue leakage and the expression of aquaporin-4(AQP-4),matrix metalloproteinase-9(MMP-9),zonula occludens-1(ZO-1)and occludin were measured.RESULTS After treatment with antiCKLF1 antibody,brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24 h after reperfusion,but not changed in contralateral hemisphere.Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9,and upregulated the expression of ZO-1 and Occludin.These results suggest that CKLF1 is involved in BBB disruption after reperfusion.CONCLUSION Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity,possibly via inhibiting the expression of AQP-4 and MMP-9,and increasing the expression of tight junction protein. 展开更多
关键词 chemokine-like factor 1 cerebral ischemia brain-blood barrier
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Nanocarriers as a powerful vehicle to overcome blood-brain barrier in treating neurodegenerative diseases: Focus on recent advances 被引量:9
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作者 Xiaoqian Niu Jiejian Chen Jianqing Gao 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2019年第5期480-496,共17页
Neurodegenerative diseases including Alzheimer’s disease,Parkinson’s disease,Huntington disease and amyotrophic lateral sclerosis throw a heavy burden on families and society. Related scientific researches make tard... Neurodegenerative diseases including Alzheimer’s disease,Parkinson’s disease,Huntington disease and amyotrophic lateral sclerosis throw a heavy burden on families and society. Related scientific researches make tardy progress. One reason is that the known pathogeny is just the tip of the iceberg. Another reason is that various physiological barriers,especially blood-brain barrier(BBB),hamper effective therapeutic substances from reaching site of action. Drugs in clinical treatment of neurodegenerative diseases are basically administered orally. And generally speaking,the brain targeting efficiency is pretty low. Nanodelivery technology brings hope for neurodegenerative diseases. The use of nanocarriers encapsulating molecules such as peptides and genomic medicine may enhance drug transport through the BBB in neurodegenerative disease and target relevant regions in the brain for regenerative processes. In this review,we discuss BBB composition and applications of nanocarriers-liposomes,nanoparticles,nanomicelles and new emerging exosomes in neurodegenerative diseases. Furthermore,the disadvantages and the potential neurotoxicity of nanocarriers according pharmacokinetics theory are also discussed. 展开更多
关键词 NEURODEGENERATIVE diseases blood-brain barrier NANOCARRIERS NEUROTOXICITY
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Matrix metalloproteinase-9 expression and blood brain barrier permeability in the rat brain after cerebral ischemia/reperfusion injury 被引量:2
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作者 Lifang Lei Xiaohong Zi Qiuyun Tu 《Neural Regeneration Research》 SCIE CAS CSCD 2008年第5期505-508,共4页
BACKGROUND: The integrity of the blood brain barrier (BBB) plays an important role in the patho-physiological process of cerebral ischemia/reperfusion injury. It has been recently observed that metalloproteinase-9 ... BACKGROUND: The integrity of the blood brain barrier (BBB) plays an important role in the patho-physiological process of cerebral ischemia/reperfusion injury. It has been recently observed that metalloproteinase-9 (MMP-9) is closely related to cerebral ischemia/reperfusion injury OBJECTIVE: This study was designed to observe MMP-9 expression in the rat brain after cerebral ischemia/reperfusion injury and to investigate its correlation to BBB permeability. DESIGN, TIME AND SETTING: This study, a randomized controlled animal experiment, was performed at the Institute of Neurobiology, Central South University between September 2005 and March 2006. MATERIALS: Ninety healthy male SD rats, aged 3-4 months, weighing 200-280 g, were used in the present study. Rabbit anti-rat MMP-9 polyclonal antibody (Boster, Wuhan, China) and Evans blue (Sigma, USA) were also used. METHODS: All rats were randomly divided into 9 groups with 10 rats in each group: normal control group, sham-operated group, and ischemia for 2 hours followed by reperfusion for 3, 6, 12 hours, 1, 2, 4 and 7 days groups. In the ischemia/reperfusion groups, rats were subjected to ischemia/reperfusion injury by suture occlusion of the right middle cerebral artery. In the sham-operated group, rats were merely subjected to vessel dissociation. In the normal control group, rats were not modeled. MAIN OUTCOME MEASURES: BBB permeability was assessed by determining the level of effusion of Evans blue. MMP-9 expression was detected by an immunohistochemical method. RESULTS: All 90 rats were included in the final analysis. BBB permeability alteration was closely correlated to ischemia/reperfusion time. BBB permeability began to increase at ischemia/reperfusion for 3 hours, then it gradually reached a peak level at ischemia/reperfusion for 1 day, and thereafter it gradually decreased. MMP-9 expression began to increase at ischemia/reperfusion for 3 hours, then gradually reached its peak level 2 days after perfusion, and thereafter it gradually decreased. CONCLUSION: MMP-9 expression increases in rat brain tissue after focal cerebral ischemia/reperfusion injury, which correlates with increased permeability of the BBB. 展开更多
关键词 ischemia/reperfusion injury matrix metalloproteinase-9 blood brain barrier
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Detrimental Effect of Electromagnetic Pulse Exposure on Permeability of In Vitro Blood-brain-barrier Model 被引量:10
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作者 ZHOU Jia Xing DING Gui Rong +3 位作者 ZHANG Jie ZHOU Yong Chun ZHANG Yan Jun GUO Guo Zhen 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2013年第2期128-137,共10页
Objective To study the effect of electromagnetic pulse (EMP) exposure on permeability of in vitro blood-brain-barrier (BBB) model. Methods An in vitro BBB model, established by co-culturing brain microvascular end... Objective To study the effect of electromagnetic pulse (EMP) exposure on permeability of in vitro blood-brain-barrier (BBB) model. Methods An in vitro BBB model, established by co-culturing brain microvascular endothelial cells (BMVEC) and astroglial cells (AC) isolated from rat brain, was exposed to EMP at 100 kV/m and 400 kV/m, respectively. Permeability of the model was assayed by measuring the transendothelial electrical resistance (TEER) and the horseradish peroxidase (HRP) transmission at different time points. Levels of BBB tight junction-related proteins were measured at O, 1, 2, 4, 8, 12, 16, 20, 24 h after EMP exposure by Western blotting. Results The TEER level was lower in BBB model group than in control group at 12 h after EMP, exposure which returned to its normal level at 24 h. The 24 h recovery process was triphasic and biphasic respectively after EMP exposure at 100 kV/m and 400 kV/m. Following exposure to 400 kV/m EMP, the HRP permeability increased at 1-12 h and returned to its normal level at 24 h. Western blotting showed that the claudin-5 and ZO-1 protein levels were changed after EMP exposure. Conclusion EMP exposure at 100 kV/m and 400 kV/m can increase the permeability of in vitro BBB model and BBB tight junction-related proteins such as ZO-1 and claudin-5 may change EMP-induced BBB permeability. 展开更多
关键词 Electromagnetic pulse blood-brain-barrier PERMEABILITY TEER HRP ZO-1 CLAUDIN-5
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Effects of Minimally Invasive Puncture and Drainage of Intracranial Hematoma on the Blood-brain Barrier in Patients with Cerebral Hemorrhage 被引量:7
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作者 黄晓江 郭守刚 王伟 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2007年第1期101-103,共3页
The effects of minimally invasive surgery on the blood-brain barrier (BBB) of 30 patients with cerebral hemorrhage were investigated. Difference of the BBB index and serum MBP concentration were assessed in 15 cases... The effects of minimally invasive surgery on the blood-brain barrier (BBB) of 30 patients with cerebral hemorrhage were investigated. Difference of the BBB index and serum MBP concentration were assessed in 15 cases of conservative treatment group and 15 cases of minimally invasive surgery group. The BBB index in minimally invasive surgery group was significantly lower than in conservative treatment group (P〈0.05), and the BBB index in the two treatment groups was significantly higher than in control group (P〈0.01). Serum MBP concentration in minimally invasive surgery group was significantly lower than in conservative treatment group (P〈0.05), and that in the two treatment groups was significantly higher than in control group (P〈0.01). It was suggested the permeability of BBB in patients with cerebral hemorrhage was increased, and BBB index and serum MBP concentration in patients with cerebral hemorrhage were increased. Minimally invasive surgery can reduce the lesion of cytotoxicity to BBB and cerebral edema. 展开更多
关键词 intracerebral hemorrhage blood-brain barrier BBB index MBP
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Statins Protect the Blood Brain Barrier Acutely after Experimental Intracerebral Hemorrhage 被引量:8
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作者 Dongmei Yang Robert A. Knight +4 位作者 Yuxia Han Kishor Karki Jianfeng Zhang Michael Chopp Donald M. Seyfried 《Journal of Behavioral and Brain Science》 2013年第1期100-106,共7页
Objectives: The goal of this study was to measure the impact of simvastatin and atorvastatin treatment on blood brain barrier (BBB) integrity after experimental intracerebral hemorrhage (ICH). Methods: Primary ICH was... Objectives: The goal of this study was to measure the impact of simvastatin and atorvastatin treatment on blood brain barrier (BBB) integrity after experimental intracerebral hemorrhage (ICH). Methods: Primary ICH was induced in 27 male Wistar rats by stereotactic injection of100mL of autologous blood into the striatum. Rats were divided into three groups (n = 9/group): 1) oral treatment (2 mg/kg) of atorvastatin, 2) oral treatment (2 mg/kg) simvastatin, or 3) phosphate buffered saline daily starting 24-hours post-ICH and continuing daily for the next 3 days. On the fourth day, the animals underwent magnetic resonance imaging (MRI) for measurements of T1sat (a marker for BBB integrity), T2 (edema), and cerebral blood flow (CBF). After MRI, the animals were sacrificed and immunohistology or Western blotting was performed. Results: MRI data for animals receiving simvastatin treatment showed significantly reduced BBB dysfunction and improved CBF in the ICH rim compared to controls (P 0.05) 4 days after ICH. Simvastatin also significantly reduced edema (T2) in the rim at 4 days after ICH (P 0.05). Both statin-treated groups demonstrated increased occludin and endothelial barrier antigen levels within the vessel walls, indicating better preservation of BBB function (P 0.05) and increased number of blood vessels (P 0.05). Conclusions: Simvastatin treatment administered acutely after ICH protects BBB integrity as measured by MRI and correlative immunohistochemistry. There was also evidence of improved CBF and reduced edema by MRI. Conversely, atorvastatin showed a non-significant trend by MRI measurement. 展开更多
关键词 INTRACEREBRAL HEMORRHAGE ATORVASTATIN OCCLUDIN SIMVASTATIN blood brain barrier
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Inhibition of the immunoproteasome LMP_(2) ameliorates ischemia/hypoxia-induced blood–brain barrier injury through the Wnt/β-catenin signalling pathway 被引量:3
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作者 Xing-Yong Chen Shao-Fen Wan +4 位作者 Nan-Nan Yao Ze-Jing Lin Yan-Guang Mao Xiao-Hua Yu Yin-Zhou Wang 《Military Medical Research》 SCIE CAS CSCD 2022年第4期404-418,共15页
Background:Disruption of the blood–brain barrier(BBB)after a stroke can lead to brain injury and neurological impairment.Previous work confirmed the involvement of the immunoproteasome subunit of low molecular mass p... Background:Disruption of the blood–brain barrier(BBB)after a stroke can lead to brain injury and neurological impairment.Previous work confirmed the involvement of the immunoproteasome subunit of low molecular mass peptide 2(LMP2)in the pathophysiology of ischemia stroke.However,the relationship between the immunoproteasome LMP2 and the BBB remains unclear.Methods:Adult male Sprague–Dawley rats were subjected to transient middle cerebral artery occlusion/reperfusion(MCAO/R).Three days before MCAO,the rats were treated with lentivirus-mediated LMP2 shRNA preparations by stereotactical injection into the ipsilateral hemispheric region.The rat brain microvascular endothelial cell(RBMVEC)line was exposed to oxygen–glucose deprivation/reperfusion(OGD/R)to mimic ischemic conditions in vitro.The RNA interference-mediated knockdown of LMP2 orβ-catenin was analysed in vivo and in vitro.Analysis of the quantity of extravasated Evans blue(EB)and cerebral fluorescent angiography were performed to evaluate the integrity of the BBB.Immunofluorescence and Western blotting were employed to detect the expression of target proteins.Cell migration was evaluated using a scratch migration assay.The results of immunofluorescence,Western blotting and cell migration were quantified using the software ImageJ(Version 1.53).Parametric data from different groups were compared using one-way ANOVA followed by the least significant difference(LSD)test.Results:Cerebral ischemia led to lower levels of structural components of the BBB such as tight junction proteins[occludin,claudin-1 and zonula occludens(ZO-1)]in the MCAO/R group compared with the sham group(P<0.001).However,inhibition of the immunoproteasome LMP2 restored the expression of these proteins,resulting in higher levels of occludin,claudin-1 and ZO-1 in the LMP2-shRNA group compared with the control-shRNA group(P<0.001).In addition,inhibition of the immunoproteasome LMP2 contributed to higher microvascular density and decreased BBB permeability[e.g.,the quantity of extravasated EB:LMP2-shRNA group(58.54±7.37)μg/g vs.control-shRNA group(103.74±4.32)μg/g,P<0.001],and promoted the upregulation of Wnt-3a andβ-catenin proteins in rats following MCAO/R.In vitro experiments,OGD/R induced marked upregulation of LMP2,proapoptotic protein Bax and cleaved caspase-3,and downregulation of occludin,claudin-1,ZO-1 and Bcl-2,as well as inhibition of the Wnt/β-catenin pathway Wnt-3a andβ-catenin proteins in RBMVECs,compared with the control group under normal culture conditions(P<0.001).However,silencing of LMP2 gene expression reversed these protein changes and promoted proliferation and migration of RBMVECs following OGD/R.Silencing ofβ-catenin by transfection of RBMVECs withβ-catenin-si RNA aggravated the downregulation of tight junction proteins,and reduced the proliferation and migration of RBMVECs following OGD/R,compared with the control-siRNA group(P<0.001).LMP2-si RNA andβ-catenin-si RNA co-transfection partly counteracted the beneficial effects of silencing LMP2-siRNA on the levels of tight junction proteins in RBMVECs exposed to OGD/R.Conclusions:This study suggests that inhibition of the immunoproteasome LMP2 ameliorates ischemia/hypoxia induced BBB injury,and that the molecular mechanism involves the immunoproteasome-regulated activation of the Wnt/β-catenin signalling pathway under ischemic conditions. 展开更多
关键词 IMMUNOPROTEASOME bloodbrain barrier Wnt/β-catenin pathway Oxygen–glucose deprivation/reperfusion Cerebral ischemia
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Potential therapeutic molecular targets for blood-brain barrier disruption after subarachnoid hemorrhage 被引量:16
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作者 Hideki Kanamaru Hidenori Suzuki 《Neural Regeneration Research》 SCIE CAS CSCD 2019年第7期1138-1143,共6页
Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial ... Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure,followed by global cerebral ischemia.Post-subarachnoid hemorrhage ischemia,tissue injuries as well as extravasated blood components and the breakdown products activate microglia,astrocytes and Toll-like receptor 4,and disrupt blood-brain barrier associated with the induction of many inflammatory and other cascades.Once blood-brain barrier is disrupted,brain tissues are directly exposed to harmful blood contents and immune cells,which aggravate brain injuries furthermore.Blood-brain barrier disruption after subarachnoid hemorrhage may be developed by a variety of mechanisms including endothelial cell apoptosis and disruption of tight junction proteins.Many molecules and pathways have been reported to disrupt the blood-brain barrier after subarachnoid hemorrhage,but the exact mechanisms remain unclear.Multiple independent and/or interconnected signaling pathways may be involved in blood-brain barrier disruption after subarachnoid hemorrhage.This review provides recent understandings of the mechanisms and the potential therapeutic targets of blood-brain barrier disruption after subarachnoid hemorrhage. 展开更多
关键词 blood-brain barrier early brain injury ENDOTHELIAL cell SUBARACHNOID HEMORRHAGE TIGHT junction inflammation matricellular protein TOLL-LIKE receptor 4 TLR4
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Correlation of vascular endothelial growth factor to permeability of blood-brain barrier and brain edema during high-altitude exposure 被引量:4
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作者 Qiquan Zhou Chang'e Liu +2 位作者 Jing Wang Yunli Wang Bo Zhou 《Neural Regeneration Research》 SCIE CAS CSCD 2009年第10期775-779,共5页
BACKGROUND: Many studies have evaluated the role of vascular endothelial growth factor (VEGF) in traumatic brain edema and hemorrhagic brain edema. OBJECTIVE: To observe the effects of VEGF expression on permeabil... BACKGROUND: Many studies have evaluated the role of vascular endothelial growth factor (VEGF) in traumatic brain edema and hemorrhagic brain edema. OBJECTIVE: To observe the effects of VEGF expression on permeability of the blood-brain barrier (BBB) during high-altitude and hypoxia exposure, and to investigate the correlation between VEGF expression and BBB permeability with regard to Evans blue staining and brain edema during high-altitude exposure. DESIGN, TIME AND SETTING: The randomized, controlled, animal study was performed at the Tanggula Etape, Central Laboratory of Chengdu Medical College, and Central Laboratory of General Hospital of Chengdu Military Area Command of Chinese PLA, China, from July 2003 to November 2004. MATERIALS: Quantitative RT-PCR kit (Sigma, USA), VEGF ELISA kit (Biosource, USA), and Evans blue (Jingchun, China) were acquired for this study. METHODS: A total of 180 Wistar rats were equally and randomly assigned to 15 groups: low-altitude (500 m), middle-altitude (2 880 m), high-altitude (4 200 m), super-high-altitude (5 000 m), 1,3, 5, 7, 9, 11, 13, 15, 17, 19, and 21 days of super high-altitude exposure. Wistar rats were exposed to various altitude gradients to establish a hypoxia model. MAIN OUTCOME MEASURES: Brain water content was calculated according to the wet-to-dry weight ratio. BBB permeability to Evans blue was determined by colorimetric method. VEGF mRNA and protein levels in brain tissues were detected using RT-PCR and double-antibody sandwich ELISA. RESULTS: Brain water content, BBB permeability to Evans blue, and VEGF mRNA and protein levels in brain tissues increased with increasing altitude and prolonged exposure to altitude. The greatest increase was determined on day 9 upon ascending 5 000 m. Simultaneously, VEGF expression positively correlated to BBB permeability of Evans blue and brain water content (r = 0.975, 0.917, P〈 0.01). CONCLUSION: Increased VEGF protein and mRNA expression was responsible for increased BBB permeability, which may be an important mechanism underlying brain edema during high-altitude exposure. 展开更多
关键词 HIGH-ALTITUDE blood-brain barrier PERMEABILITY vascular endothelial growth factor
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Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injury 被引量:17
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作者 Luigi Aloe Patrizia Bianchi +2 位作者 Alberto De Bellis Marzia Soligo Maria Luisa Rocco 《Neural Regeneration Research》 SCIE CAS CSCD 2014年第10期1025-1030,共6页
The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could... The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an in-creased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deifcits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells. 展开更多
关键词 nerve regeneration spinal cord injury nerve growth factor intranasal delivery blood-brain barrier motor function LEPTIN NEUROPROTECTION rats neural regeneration
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In vitro model of the blood-brain barrier established by co-culture of primary cerebral microvascular endothelial and astrocyte cells 被引量:7
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作者 Yan Wang Ning Wang +3 位作者 Biao Cai Guang-yun Wang Jing Li Xing-xing Piao 《Neural Regeneration Research》 SCIE CAS CSCD 2015年第12期2011-2017,共7页
Drugs for the treatment and prevention of nervous system diseases must permeate the bloodbrain barrier to take effect.In vitro models of the blood-brain barrier are therefore important in the investigation of drug per... Drugs for the treatment and prevention of nervous system diseases must permeate the bloodbrain barrier to take effect.In vitro models of the blood-brain barrier are therefore important in the investigation of drug permeation mechanisms.However,to date,no unified method has been described for establishing a blood-brain barrier model.Here,we modified an in vitro model of the blood-brain barrier by seeding brain microvascular endothelial cells and astrocytes from newborn rats on a polyester Transwell cell culture membrane with 0.4-μm pores,and conducted transepithelial electrical resistance measurements,leakage tests and assays for specific bloodbrain barrier enzymes.We show that the permeability of our model is as low as that of the bloodbrain barrier in vivo.Our model will be a valuable tool in the study of the mechanisms of action of neuroprotective drugs. 展开更多
关键词 nerve regeneration blood-brain barrier ASTROCYTES brain microvascular endothelial cells permeability CO-CULTURE Transwell chamber neural regeneration
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Synaptic and blood-brain barrier structural changes in a rat epilepsy model induced by coriaria lacton Replication experiment with animals 被引量:2
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作者 Jiyan Cheng Jichun Huang +3 位作者 Yi Han Guangyi Liu Ling Yin Furong Zheng 《Neural Regeneration Research》 SCIE CAS CSCD 2008年第1期25-28,共4页
BACKGROUND: Structural and functional synaptic changes, as well as blood-brain barrier (BBB) changes, affect the micro-environment of nervous tissue and excitation, both of which play an important role in epilepsy.... BACKGROUND: Structural and functional synaptic changes, as well as blood-brain barrier (BBB) changes, affect the micro-environment of nervous tissue and excitation, both of which play an important role in epilepsy. OBJECTIVE: To observe synaptic and BBB ultrastructural changes in the motor cortex of a rat epilepsy model induced by coriaria lacton, and to investigate the synaptic and BBB effects on the mechanism of epilepsy. DESIGN: A randomized controlled animal experiment. SETTING: Department of Histology and Embryology, Luzhou Medical College; and Electron Microscopy Laboratory, Luzhou Medical College. MATERIALS: Twenty healthy male Sprague Dawley rats, aged 8 weeks, were chosen for this study. The rats weighed (280 ± 50) g and were supplied by the Experimental Animal Center of Luzhou Medical College. Experimentation was performed in accordance with the ethical guidelines for the use and care of animals. The animals were randomly divided into a control group and an epilepsy group, with 10 rats in each group. METHODS: This study was performed at the Department of Histology and Embryology, and Electron Microscopy Laboratory, Luzhou Medical College between February and December 2006. According to the protocol, the epilepsy group was injected with 10 μ L/100 g coriaria lacton into the lateral ventricles to establish an epileptic model. The control group rats were not administered anything. Eight days after the model was established, all rats were anesthetized with ether. The motor cortex was removed and sectioned into ultrathin sections. Synaptic and BBB ultrastructural changes were observed by electron microscopy. MAIN OUTCOME MEASURES: (1)Structural changes of three different parts of the synapses, synaptic cleft width, postsynaptic density thickness, proportion of perforation synapses, curvature of synaptic interface, and length of active zones. (2)Capillary and BBB changes (endothelium, basement membrane, pericyte, and the astrocyte endfeet). RESULTS: (1)Curvature of synaptic interface, length of active zones, thickness of postsynaptic density, and percentage of perforation synapses increased significantly. (2)There was significant edema in the endothelium, basement membrane, and the pericyte of the epilepsy group; the electron density of the basement membrane was reduced. CONCLUSION: (1) The coriaria lacton treatment altered synaptic ultrastructure, as well as BBB characteristics, in the epileptic rat model, and also improved synaptic transmission efficiency, as well as BBB permeability; (2)Synaptic and BBB ultrastructural changes might play an important role in the mechanism of epilepsy. 展开更多
关键词 coriaria lacton EPILEPSY SYNAPSE blood-brain barrier rats
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Identification of blood-brain barrier function following subarachnoid hemorrhage in rats at different stages 被引量:2
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作者 Zongyi Xie Weiwei Shen +1 位作者 Ying Ma Yuan Cheng 《Neural Regeneration Research》 SCIE CAS CSCD 2008年第4期444-448,共5页
BACKGROUND: Recent studies have indicated that blood-brain barrier (BBB) disruption following subarachnoid hemorrhage (SAH) significantly correlates with the development of brain injury and poor prognosis of pati... BACKGROUND: Recent studies have indicated that blood-brain barrier (BBB) disruption following subarachnoid hemorrhage (SAH) significantly correlates with the development of brain injury and poor prognosis of patients subjected to SAH. OBJECTIVE: To investigate both functional and structural changes related to BBB in various phases after SAH in rats through quantitative and qualitative methods. DESIGN, TIME AND SETTING: This experiment, a completely randomized design and controlled experiment, was performed at the Department of Neurosurgery, the Second Affiliated Hospital of Chongqing University of Medical Sciences from June 2006 to March 2007. MATERIALS: A total of 128 female, healthy, Sprague-Dawley rats were selected for this study. Main reagents and instruments: Evans Blue dye (Sigma Company, USA), fluorescence spectrophotometer (Shimadzu Company, Japan), and transmission electron microscope (Olympus Company, Japan). METHODS: The included 128 rats were randomly divided into two groups: sham-operated group (n = 16) and SAH group (n = 112). Rats in the SAH group were divided into seven subgroups: 6, 12, 24, 36, 48, 60, and 72 hours after SAH (16 rats for each time point). Experimental SAH was induced by blood injection into the pre-chiasmatic cistern (300 μ L). The sham-operated group received an equivalent volume of normal saline solution (300 μ L) injected into the subarachnoid space. MAIN OUTCOME MEASURES: Brain tissue water content was determined by the wet-dry method. BBB permeability in the cerebral cortex was determined by Evans Blue dye and fluorescent spectrophotometer. The ultrastructural changes in BBB were observed with transmission electron microscope. RESULTS: Compared with the sham-operated group, SAH induced a significant increase in brain water content between 24 and 60 hours (F = 888.32, P 〈 0.05). Brain water content increased to a maximum by 36 hours after SAH, normalizing by 72 hours. Evans Blue content in the cerebral cortex of SAH group rats began to increase by 24 hours after SAH, peaked at 36 hours (F = 896.72, P 〈 0.05), and significantly decreased at later observation times, finally normalizing by 72 hours after SAH (P 〉 0.05). Electron microscopy demonstrated only a mild perivascular edema at 24 hours after SAH. By 36 hours, a notable perivascular edema was associated with a collapse of the capillary. Astrocytic endfeet surrounding the capillary were prominently swollen in the edematous areas. The above-mentioned abnormal ultrastructural changes in the BBB were reversed by 72 hours after SAH. No obvious morphological changes in the BBB were detected in the sham-operated rats. CONCLUSION: These results directly suggest that SAH could induce rapid changes in BBB function and structure during the acute phases of BBB breakdown. Moreover, these dynamic alterations further indicate that the BBB possesses the ability to self-repair. BBB dysfunction plays an important role in the development of vasogenic edema and unfavorable outcome. 展开更多
关键词 subarachnoid hemorrhage blood-brain barrier RATS
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Aquaporin 4 expression and ultrastructure of the blood-brain barrier following cerebral contusion injury 被引量:4
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作者 Xinjun Li Yangyun Han +5 位作者 Hong Xu Zhongshu Sun Zengjun Zhou Xiaodong Long Yumin Yang Linbo Zou 《Neural Regeneration Research》 SCIE CAS CSCD 2013年第4期338-345,共8页
This study aimed to investigate aquaporin 4 expression and the ultrastructure of the blood-brain barrier at 2-72 hours following cerebral contusion injury, and correlate these changes to the formation of brain edema. ... This study aimed to investigate aquaporin 4 expression and the ultrastructure of the blood-brain barrier at 2-72 hours following cerebral contusion injury, and correlate these changes to the formation of brain edema. Results revealed that at 2 hours after cerebral contusion and laceration injury, aquaporin 4 expression significantly increased, brain water content and blood-brain barrier permeability increased, and the number of pinocytotic vesicles in cerebral microvascular endothelia cells increased. In addition, the mitochondrial accumulation was observed. As contusion and laceration injury became aggravated, aquaporin 4 expression continued to increase, brain water content and blood-brain barrier permeability gradually increased, brain capillary endothelial cells and astrocytes swelled, and capillary basement membrane injury gradually increased. The above changes were most apparent at 12 hours after injury, after which they gradually attenuated. Aquaporin 4 expression positively correlated with brain water content and the blood-brain barrier index. Our experimental findings indicate that increasing aquaporin 4 expression and blood-brain barrier permeability after cerebral contusion and laceration injury in humans is involved in the formation of brain edema. 展开更多
关键词 neural regeneration brain injury cerebral contusion and laceration injury aquaporin 4 blood-brain barrier ULTRASTRUCTURE brain edema human early stage photographs-containing paper NEUROREGENERATION
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Controllable blood–brain barrier(BBB)regulation based on gigahertz acoustic streaming 被引量:1
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作者 Hang Qi Shuaihua Zhang +2 位作者 Jiaxue Liang Shan He Yanyan Wang 《Nanotechnology and Precision Engineering》 CAS CSCD 2022年第4期1-7,共7页
The blood–brain barrier(BBB)is a structural and functional barrier necessary for brain homeostasis,and it plays an important role in the realization of neural function and in protecting the brain from damage by circu... The blood–brain barrier(BBB)is a structural and functional barrier necessary for brain homeostasis,and it plays an important role in the realization of neural function and in protecting the brain from damage by circulating toxins and pathogens.However,the extremely dense BBB also severely limits the transport of molecules across it,which is a great hindrance to the diagnosis and treatment of central nervous system(CNS)diseases.This paper reports a new method for controllable opening of the BBB,based on the gigahertz acoustic streaming(AS)generated by a bulk acoustic wave resonant device.By adjusting the input power and working distance of the device,AS with tunable flow rate can be generated to disrupt tight junction proteins(TJs)between endothelial cells.The results obtained with this method show that the gigahertz AS promotes the penetration of dextran molecules with different molecular weights across the BBB.This work provides a new platform for studying the mechanical regulation of BBB by fluid shear forces and a new method for improving the efficiency of drug delivery. 展开更多
关键词 bloodbrain barrier Mechanical regulation Drug delivery Bulk acoustic wave Acoustic streaming
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Electroacupuncture reduces injury to the blood-brain barrier following cerebral ischemia/reperfusion injury 被引量:7
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作者 Yongjun Peng Hesheng Wang +3 位作者 Jianhua Sun Li Chen Meijuan Xu Jihong Chu 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第36期2901-2906,共6页
This study used electroacupuncture at Renzhong (DU26) and Baihui (DU20) in a rat model of cerebral ischemia/reperfusion injury. Neurological deficit scores, western blotting, and reverse transcription-PCR results ... This study used electroacupuncture at Renzhong (DU26) and Baihui (DU20) in a rat model of cerebral ischemia/reperfusion injury. Neurological deficit scores, western blotting, and reverse transcription-PCR results demonstrated that electroacupuncture markedly reduced neurological deficits, decreased corpus striatum aquaporin-4 protein and mRNA expression, and relieved damage to the blood-brain barrier in a rat model of cerebral ischemia/reperfusion injury. These results suggest that electroacupuncture most likely protects the blood-brain barrier by regulating aquaporin-4 expression following cerebral ischemia/reperfusion injury. 展开更多
关键词 ELECTROACUPUNCTURE cerebral ischemia/reperfusion blood-brain barrier AQUAPORIN-4 brain edema rat Renzhong (DU26) Baihui (DU20) brain injury regeneration neural regeneration
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Effects of Yishendaluo decoction on blood-brain barrier integrity in mice with experimental autoimmune encephalomyelitis 被引量:2
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作者 Yanqing Wu Ying Gao +4 位作者 Lingqun Zhu Yonghong Gao Dongmei Zhang Lixia Lou Yanfang Yan 《Neural Regeneration Research》 SCIE CAS CSCD 2011年第15期1151-1157,共7页
This study investigated the effects of Yishendaluo decoction on the loss of blood-brain barrier integrity in mice exhibiting experimental autoimmune encephalomyelitis.To this end,we used real-time fluorescent quantita... This study investigated the effects of Yishendaluo decoction on the loss of blood-brain barrier integrity in mice exhibiting experimental autoimmune encephalomyelitis.To this end,we used real-time fluorescent quantitative PCR to measure the levels of mRNAs specific to the T cell markers CD4 and CD8,and the monocyte marker CD11b.In addition,we used Evans blue dye extravasation in the spinal cord and brain tissues to assess blood-brain barrier permeability.The results indicated that an increase in blood-brain barrier permeability was associated with an increase in CD4,CD8 and CD11b mRNA expression in experimental autoimmune encephalomyelitis mice.Yishendaluo decoction administration significantly reversed inflammatory cell accumulation in cerebral tissues of experimental autoimmune encephalomyelitis mice. 展开更多
关键词 experimental autoimmune encephalomyelitis Yishendaluo decoction blood-brain barrier neurological score spinal cord
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The effects of aerobic exercise training on oxidant-antioxidant balance, neurotrophic factor levels, and blood-brain barrier function in obese and non-obese men 被引量:2
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作者 Hee-Tae Roh Wi-Young So 《Journal of Sport and Health Science》 SCIE 2017年第4期447-453,共7页
Purpose: The purpose of this study was to investigate the effects of obesity and aerobic exercise training on oxidant-antioxidant balance,neurotrophic factor levels, and blood-brain barrier(BBB) function.Methods: Ten ... Purpose: The purpose of this study was to investigate the effects of obesity and aerobic exercise training on oxidant-antioxidant balance,neurotrophic factor levels, and blood-brain barrier(BBB) function.Methods: Ten non-obese healthy men(body mass index < 25 kg/m2) and 10 obese men(body mass index ≥ 25 kg/m2) were included in the study.Both groups performed treadmill exercise for 40 min 3 times weekly for 8 weeks at 70% heart rate reserve. Blood samples were collected to examine oxidant-antioxidant balance(reactive oxygen species(ROS) and superoxide dismutase(SOD) activity levels), neurotrophic factors(brain-derived neurotrophic factor(BDNF), nerve growth factor, and glial cell line-derived neurotrophic factor levels), and BBB function(S100βand neuron-specific enolase(NSE) levels) before and after exercise training.Results: The obese group showed significantly greater changes than the non-obese group in serum ROS(-0.46 ± 0.31 mmol/L vs.-0.10 ±0.17 mmol/L,p=0.005),serum S100 p levels(-8.50 ± 5.92 ng/L vs.-0.78 ± 5.45 ng/L,p=0.007),and serum NSE levels(-0.89 ± 0.54 μg/L vs.-0.01 ± 0.74 μg/L,p= 0.007) after training. At baseline,the obese group showed significantly higher serum ROS and S100β levels and significantly lower serum SOD activity and BDNF levels than the non-obese group(p < 0.05). The obese group showed significantly lower serum ROS, S100β,and NSE levels and significantly higher serum SOD activity and BDNF levels after training compared with baseline(p < 0.05).Conclusion: These results suggest that obesity can reduce serum neurotrophic factor levels and can induce BBB dysfunction. On the other hand,aerobic exercise can improve an oxidant-antioxidant imbalance in obese subjects and limit BBB dysfunction. 展开更多
关键词 blood-brain barrier Exercise training Neurotrophic factor OBESITY Oxidative stress Redox balance
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