The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the bloo...The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood.The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function.It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain barrier.Furthermore,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier.This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability.This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date.This will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic monitoring.In addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progre展开更多
Glioblastoma multiforme(GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as w...Glioblastoma multiforme(GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as well as the presence of the blood–brain barrier(BBB), have reduced the efficacy of GBM treatment. The emergence of a novel therapeutic method, namely, sonodynamic therapy(SDT), provides a promising strategy for eradicating tumors via activated sonosensitizers coupled with low-intensity ultrasound. SDT can provide tumor killing effects for deep-seated tumors, such as brain tumors. However, conventional sonosensitizers cannot effectively reach the tumor region and kill additional tumor cells, especially brain tumor cells. Efforts should be made to develop a method to help therapeutic agents pass through the BBB and accumulate in brain tumors. With the development of novel multifunctional nanosensitizers and newly emerging combination strategies, the killing ability and selectivity of SDT have greatly improved and are accompanied with fewer side effects. In this review, we systematically summarize the findings of previous studies on SDT for GBM, with a focus on recent developments and promising directions for future research.展开更多
血脑屏障(blood-brain barrier,BBB)是介于外周和中枢神经系统之间的一道生理屏障,对维持中枢神经系统的稳态起着重要作用。研究表明,血脑屏障与阿尔茨海默病(Alzheimer’s disease,AD)的发生发展密切相关。该文重点论述血脑屏障晚期糖...血脑屏障(blood-brain barrier,BBB)是介于外周和中枢神经系统之间的一道生理屏障,对维持中枢神经系统的稳态起着重要作用。研究表明,血脑屏障与阿尔茨海默病(Alzheimer’s disease,AD)的发生发展密切相关。该文重点论述血脑屏障晚期糖基化终产物受体(receptor for advanced glycation end products,RAGE)/低密度脂蛋白受体相关蛋白1(low density lipoprotein receptor-related protein 1,LRP1)受体转运系统及以血脑屏障为核心组分的神经血管单元(neurovascular unit,NVU)介导的中枢β-淀粉样蛋白(β-amyloid protein,Aβ)水平调控与AD发病机制的关系,为AD防治提供新思路。展开更多
背景与目的:开放血脑屏障将为胶质瘤的综合治疗提供新的希望,本研究观察C6脑胶质瘤不同区域血-脑屏障(BBB)的通透性的变化、超微结构特征及紧密连接蛋白claudin-5的表达变化。方法:雄性SD大鼠,随机分为对照组和荷瘤组,采用立体定向方法...背景与目的:开放血脑屏障将为胶质瘤的综合治疗提供新的希望,本研究观察C6脑胶质瘤不同区域血-脑屏障(BBB)的通透性的变化、超微结构特征及紧密连接蛋白claudin-5的表达变化。方法:雄性SD大鼠,随机分为对照组和荷瘤组,采用立体定向方法在大鼠右侧尾状核接种C6细胞建立大鼠C6胶质瘤模型,于建模后第20天取肿瘤、肿瘤临近处(brain adjacent to tumor,BAT)即距肿瘤边界2mm以内及肿瘤远隔处(brain dis-tant to tumor,BDT)即2mm以外的大脑半球脑皮质3个部位的脑组织和对照鼠右侧尾状核正常脑组织,采用外源性硝酸镧透射电镜示踪法,观察BBB/BBTB超微结构特征;免疫组化法观察紧密连接蛋白claudin-5在正常鼠和荷瘤鼠各部位的表达变化。结果:(1)肿瘤处可见La3+通过血管内皮细胞的紧密连接渗透至血管腔外及脑间质裂隙内,BAT部分见La3+渗出至局部基底膜,大部分分布在血管腔内,而BDT及对照组正常脑组织La3+分布在血管腔内,血管内皮细胞紧密连接结构完整,基底膜呈线状连续,脑血管内皮细胞浆均未见La3+。(2)claudin-5在BDT与对照组脑组织表达丰富、连续;肿瘤处表达减弱,沿血管呈间断表达;BAT较正常脑组织表达下降,但仍呈连续状态。结论:正常脑组织血脑屏障稳定,通透性最低;肿瘤的周边存在不同程度的屏障;C6胶质瘤细胞的直接浸润可以降低内皮细胞紧密连接蛋白claudin-5,可能是诱导紧密连接破坏导致BBTB通透性增高的重要原因。展开更多
基金supported by the National Natural Science Foundation of China,No.82104412(to TD)Shaanxi Provincial Key R&D Program,No.2023-YBSF-165(to TD)+1 种基金the Natural Science Foundation of Shaanxi Department of Science and Technology,No.2018JM7022(to FM)Shaanxi Provincial Key Industry Chain Project,No.2021ZDLSF04-11(to PW)。
文摘The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood.The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function.It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain barrier.Furthermore,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier.This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability.This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date.This will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic monitoring.In addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progre
基金partially supported by the National Natural Science Foundation of China(81702457)the Clinical Medical University and Hospital Joint Construction of Disciplinary Projects 2021(2021lcxk017)+4 种基金the Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer(2020B121201004)the Outstanding Youths Development Scheme of Nanfang Hospital,Southern Medical University(2021J008)the Basic and Clinical Cooperative Research and Promotion Program of Anhui Medical University(2021xkjT028)the Open Fund of Key Laboratory of Antiinflammatory and Immune Medicine(KFJJ-2021-11)Grants for Scientific Research of BSKY from Anhui Medical University(1406012201)。
文摘Glioblastoma multiforme(GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as well as the presence of the blood–brain barrier(BBB), have reduced the efficacy of GBM treatment. The emergence of a novel therapeutic method, namely, sonodynamic therapy(SDT), provides a promising strategy for eradicating tumors via activated sonosensitizers coupled with low-intensity ultrasound. SDT can provide tumor killing effects for deep-seated tumors, such as brain tumors. However, conventional sonosensitizers cannot effectively reach the tumor region and kill additional tumor cells, especially brain tumor cells. Efforts should be made to develop a method to help therapeutic agents pass through the BBB and accumulate in brain tumors. With the development of novel multifunctional nanosensitizers and newly emerging combination strategies, the killing ability and selectivity of SDT have greatly improved and are accompanied with fewer side effects. In this review, we systematically summarize the findings of previous studies on SDT for GBM, with a focus on recent developments and promising directions for future research.
文摘血脑屏障(blood-brain barrier,BBB)是介于外周和中枢神经系统之间的一道生理屏障,对维持中枢神经系统的稳态起着重要作用。研究表明,血脑屏障与阿尔茨海默病(Alzheimer’s disease,AD)的发生发展密切相关。该文重点论述血脑屏障晚期糖基化终产物受体(receptor for advanced glycation end products,RAGE)/低密度脂蛋白受体相关蛋白1(low density lipoprotein receptor-related protein 1,LRP1)受体转运系统及以血脑屏障为核心组分的神经血管单元(neurovascular unit,NVU)介导的中枢β-淀粉样蛋白(β-amyloid protein,Aβ)水平调控与AD发病机制的关系,为AD防治提供新思路。
文摘背景与目的:开放血脑屏障将为胶质瘤的综合治疗提供新的希望,本研究观察C6脑胶质瘤不同区域血-脑屏障(BBB)的通透性的变化、超微结构特征及紧密连接蛋白claudin-5的表达变化。方法:雄性SD大鼠,随机分为对照组和荷瘤组,采用立体定向方法在大鼠右侧尾状核接种C6细胞建立大鼠C6胶质瘤模型,于建模后第20天取肿瘤、肿瘤临近处(brain adjacent to tumor,BAT)即距肿瘤边界2mm以内及肿瘤远隔处(brain dis-tant to tumor,BDT)即2mm以外的大脑半球脑皮质3个部位的脑组织和对照鼠右侧尾状核正常脑组织,采用外源性硝酸镧透射电镜示踪法,观察BBB/BBTB超微结构特征;免疫组化法观察紧密连接蛋白claudin-5在正常鼠和荷瘤鼠各部位的表达变化。结果:(1)肿瘤处可见La3+通过血管内皮细胞的紧密连接渗透至血管腔外及脑间质裂隙内,BAT部分见La3+渗出至局部基底膜,大部分分布在血管腔内,而BDT及对照组正常脑组织La3+分布在血管腔内,血管内皮细胞紧密连接结构完整,基底膜呈线状连续,脑血管内皮细胞浆均未见La3+。(2)claudin-5在BDT与对照组脑组织表达丰富、连续;肿瘤处表达减弱,沿血管呈间断表达;BAT较正常脑组织表达下降,但仍呈连续状态。结论:正常脑组织血脑屏障稳定,通透性最低;肿瘤的周边存在不同程度的屏障;C6胶质瘤细胞的直接浸润可以降低内皮细胞紧密连接蛋白claudin-5,可能是诱导紧密连接破坏导致BBTB通透性增高的重要原因。
