血脑屏障损伤诱发神经病变的评估方法及机制研究进展
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摘要
血脑屏障(BBB)是人体的生理屏障结构,发挥维持中枢神经系统内环境稳定的重要作用。中枢神经系统疾病如颅脑创伤、颅内肿瘤和神经退行性病变等均可以引起血脑屏障的损害。此外,血脑屏障损伤可以诱发中枢神经系统病变。目前,缺乏简明精确的血脑屏障评估手段成为中枢神经病变临床实践和研究的一个限制性因素。因此,血脑屏障评估技术及其完整性对中枢神经系统病变的意义十分重要。
The blood-brain barrier( BBB) is a significant physiological barrier separately the central neural system with peripheral blood circulation.It plays an essential role in maintaining the brain homeostasis. Many neurological conditions are accompanied with blood-brain barrier disruption( e. g. traumatic brain injury,intracranial tumor,chronic neurodegenerative disorders).Recently many experiments have suggested that the blood-brain barrier disruption may be a cause rather than just a result from brain damage which suggested that the BBB is an important therapeutic target.However,the current lack of concise and accurate blood-brain barrier assessment has become a limiting factor in the clinical practice and research of central neuropathy.
The blood-brain barrier( BBB) is a significant physiological barrier separately the central neural system with peripheral blood circulation.It plays an essential role in maintaining the brain homeostasis. Many neurological conditions are accompanied with blood-brain barrier disruption( e. g. traumatic brain injury,intracranial tumor,chronic neurodegenerative disorders).Recently many experiments have suggested that the blood-brain barrier disruption may be a cause rather than just a result from brain damage which suggested that the BBB is an important therapeutic target.However,the current lack of concise and accurate blood-brain barrier assessment has become a limiting factor in the clinical practice and research of central neuropathy.
引文
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[2]Andreone BJ,Chow BW,Tata A,et al.Blood-brain barrier permeability is regulated by lipid transport-dependent suppression of caveolae-mediated transcytosis[J].Neuron,2017,94:581-594.
[3]Paul D,Cowan AE,Ge S,et al.Novel 3D analysis of Claudin-5 reveals significant endothelial heterogeneity among CNS microvessels[J].Microvasc Res,2013,86:1-10.
[4]Mittapalli RK,Adkins CE,Bohn KA,et al.Quantitative fluorescence microscopy measures vascular pore size in primary and metastatic brain tumors[J].Cancer Res,2017,77:238-246.
[5]Gurnik S,Devraj K,Macas J,et al.Angiopoietin-2-induced blood-brain barrier compromise and increased stroke size are rescued by VE-PTP-dependent restoration of Tie2 signaling[J].Acta Neuropathol,2016,131:753-773.
[6]Ziegler N,Awwad K,Fisslthaler B,et al.beta-Catenin is required for endothelial Cyp1b1 regulation influencing metabolic Barrier Function[J].J Neurosci,2016,36:8921-8935.
[7]Vutukuri R,Brunkhorst R,Kestner RI,et al.Alteration of sphingolipid metabolism as a putative mechanism underlying LPS-induced BBB disruption[J].J Neurochem,2018,144:172-185.
[8]Xu Y,Cui H,Zhu Q,et al.Unilateral opening of rat blood-brain barrier assisted by diagnostic ultrasound targeted microbubbles destruction[J].Biomed Res Int,2016,2016:4759750.doi:10.1155/2016/4759750.
[9]Kirchhoff C,Buhmann S,Braunstein V,et al.Cerebrospinal s100-B:a potential marker for progressive intracranial hemorrhage in patients with severe traumatic brain injury[J].Eur J Med Res,2008,13:511-516.
[10]Shi Y,Zhang L,Pu H,et al.Rapid endothelial cytoskeletal reorganization enables early blood-brain barrier disruption and long-term ischaemic reperfusion brain injury[J].Nat Commun,2016,7:10523.doi:10.1038/ncomms10523.
[11]Bernard SC,Simpson N,Join-Lambert O,et al.Pathogenic neisseria meningitidis utilizes CD147 for vascular colonization[J].Nat Med.2014,20:725-731.
[12]Frister A,Schmidt C,Schneble N,et al.Phosphoinositide3-kinase gamma affects LPS-induced disturbance of bloodbrain barrier via lipid kinase-independent control of c AMPin microglial cells[J].Neuromolecular Med,2014,16:704-713.
[13]Hoyer C,Eisele P,Ebert AD,et al.Blood-CSF-barrier dysfunction is a marker for encephalitic involvement in patients with aseptic meningitis/meningoencephalitis[J].JClin Virol,2016,84:82-86.
[14]Arba F,Leigh R,Inzitari D,et al.Blood-brain barrier leakage increases with small vessel disease in acute ischemic stroke[J].Neurology,2017,89:2143-2150.
[15]Badaut J,Ajao DO,Sorensen DW,et al.Caveolin expression changes in the neurovascular unit after juvenile traumatic brain injury:signs of blood-brain barrier healing?[J].Neuroscience,2015,285:215-226.
[16]Matsumoto J,Stewart T,Sheng L,et al.Transmission of alpha-synuclein-containing erythrocyte-derived extracellular vesicles across the blood-brain barrier via adsorptive mediated transcytosis:another mechanism for initiation and progression of Parkinson's disease?[J].Acta Neuropathol Commun,2017,5:71.doi:10.1186/S40478-017-0470-4.
[17]Devraj K,Poznanovic S,Spahn C,et al.BACE-1 is expressed in the blood-brain barrier endothelium and is upregulated in a murine model of Alzheimer's disease[J].JCereb Blood Flow Metab,2016,36:1281-1294.
[18]Hosono J,Morikawa S,Ezaki T,et al.Pericytes promote abnormal tumor angiogenesis in a rat RG2 glioma model[J].Brain Tumor Pathol,2017,34:120-129.
[19]Leuthardt EC,Duan C,Kim MJ,et al.Hyperthermiclaser ablation of recurrent glioblastoma leads to temporary disruption of the peritumoral blood brain barrier[J].PLoSOne,2016,11:e148613.doi:10.1371/journal.pone.0148613.
[20]Baghirov H,Snipstad S,Sulheim E,et al.Ultrasoundmediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model[J].PLoS One,2018,13:e191102.doi:10.1371/journal.pone.0191102.