切换至 "中华医学电子期刊资源库"

中华脑血管病杂志(电子版) ›› 2021, Vol. 15 ›› Issue (05) : 276 -280. doi: 10.11817/j.issn.1673-9248.2021.05.001

专家论坛

脑细胞外间隙与缺血性脑卒中的研究进展
蔡宪杰1, 高亚娟2, 傅瑜3,()   
  1. 1. 100191 北京大学第三医院放射科;100191 北京市磁共振成像与技术重点实验室
    2. 100191 北京大学第三医院放射科
    3. 100191 北京大学第三医院神经内科
  • 收稿日期:2021-08-04 出版日期:2021-10-09
  • 通信作者: 傅瑜

Research progress of brain extracellular space and ischemic stroke

Xianjie Cai1, Yajuan Gao2, Yu Fu3,()   

  1. 1. Department of Radiology, Peking University Third Hospital, Beijing 100191, China; Beijing Key Lab of Magnetic Resonance Imaging Device and Technique, Beijing 100191, China
    2. Department of Radiology, Peking University Third Hospital, Beijing 100191, China
    3. Department of Neurology, Peking University Third Hospital, Beijing 100191, China
  • Received:2021-08-04 Published:2021-10-09
  • Corresponding author: Yu Fu
引用本文:

蔡宪杰, 高亚娟, 傅瑜. 脑细胞外间隙与缺血性脑卒中的研究进展[J]. 中华脑血管病杂志(电子版), 2021, 15(05): 276-280.

Xianjie Cai, Yajuan Gao, Yu Fu. Research progress of brain extracellular space and ischemic stroke[J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2021, 15(05): 276-280.

脑卒中是严重影响我国国民健康的重大疾病。由于人口老龄化的加重以及饮食结构的变化,其发病率逐年升高。脑卒中类型以缺血性脑卒中为主。长期以来,缺血性脑卒中的药物治疗一直以血管系统给药为主。脑细胞外间隙(ECS)是存在于脑细胞间及细胞与血管之间的狭窄空隙,与各类脑细胞直接接触,为脑细胞生存及行使功能提供微环境,是潜在的缺血性脑卒中治疗途径。升级的脑ECS结构探索技术使全脑范围活体检测脑ECS结构及其内的物质转运成为了可能,通过脑ECS途径治疗缺血性脑卒中成为可以实现的治疗策略。本文就脑ECS的概念及其在缺血性脑卒中发生后的变化以及经该途径给药治疗缺血性脑卒中的最新突破进行综述。

Stroke is a major disease that seriously affects the health of our nationals. Due to the aggravation of population aging and changes in diet structure, the incidence of stroke is increasing gradually. Ischemic stroke is the major type of stroke. For a long time, the drug treatment of stroke has been taken dominantly via the vascular system, with limited success. The brain extracellular space (ECS) is a narrow space between brain cells and blood vessels. The brain ECS is directly contacted with various types of brain cells, providing a microenvironment for the survival and functioning of brain cells, which is potential treatment pathway for ischemic stroke. The upgraded brain ECS exploration technology makes it possible to detect the structure of brain ECS and the substance transportation within the whole brain in vivo. The treatment of ischemic stroke through the brain ECS approach has become an achievable treatment strategy. This article reviews the concept of brain ECS and its changes after ischemic stroke, as well as the latest breakthroughs in the treatment of ischemic stroke through this route.

表1 脑细胞间液引流与间质系统定量分析方法的原理及技术性能指标比较
表2 脑细胞外间隙几何结构和细胞间液引流的生物物理学参数
1
王拥军, 李子孝, 赵继宗, 等. 中国卒中报告2019(中文版)(1) [J]. 中国卒中杂志, 2020, 15(10): 1037-1043..
2
Wu S, Wu B, Anderson CS, et al. Stroke in China: advances and challenges in epidemiology, prevention, and management [J] . Lancet Neurol, 2019, 18(4): 394-405.
3
Gao Y, Jiang B, Sun H, et al. The burden of stroke in China: results from a nationwide population-based epidemiological survey [J]. PloS One, 2018, 13(12): e0208398.
4
《中国脑卒中防治报告》编写组. 《中国脑卒中防治报告2019》概要 [J]. 中国脑血管病杂志, 2020, 17(5): 272-281.
5
蔡婧婧, 雷志浩, 任力杰, 等. 卒中救治和质量控制体系的建设与研究进展 [J]. 中国卒中杂志, 2021, 16(1): 1-5.
6
Fukuta T, Ishii T, Oku N, et al. Applications of liposomal drug delivery systems to develop neuroprotective agents for the treatment of ischemic stroke [J]. Biol Pharm Bull, 2019, 42(3): 319-326.
7
Hong SB, Yang H, Hu Q, et al. Potential of exosomes for the treatment of stroke [J]. Cell Transplant, 2019, 28(6): 662-670.
8
Patel MM, Patel BM. Crossing the blood-brain barrier: recent advances in drug delivery to the brain [J]. CNS Drugs, 2017, 31(2): 109-133.
9
Tsou YH, Zhang XQ, Xu X , et al. Drug delivery to the brain across the blood-brain barrier using nanomaterials [J]. Small, 2018, 14(25): e1801588.
10
Lei Y, Han H, Zhao Y, et al. The brain interstitial system: anatomy, modeling, in vivo measurement, and applications [J]. Prog Neurobiol, 2017, 157: 230-246.
11
Odackal J, Colbourn R, Hrabetova S, et al. Real-time iontophoresis with tetramethylammonium to quantify volume fraction and tortuosity of brain extracellular space [J]. Vis Exp, 2017(125): 55755
12
Shetty AK, Zanirati G. The interstitial system of the brain in health and disease [J]. Aging Dis, 2020, 11(1): 200-211.
13
Bergsneider M. Evolving concepts of cerebrospinal fluid physiology [J]. Neurosurg Clin N Am, 2001, 12(4): 631-638.
14
Edsbagge M, Tisell M, Wikkelso C, et al. Spinal CSF absorption in healthy individuals [J]. Am J Physiol Regul Integr Comp Physiol, 2004, 287(6): 1450-1455.
15
Milhorat TH. The third circulation revisited [J]. Neurosurg, 1975, 42(6): 628-645.
16
Bonneh-Barkay D, Wiley CA. Brain extracellular matrix in neurodegeneration [J]. Brain Pathol, 2009, 19(4): 573-585.
17
Nicholson C, Hrabětová S. Brain extracellular space: the final frontier of neuroscience [J]. Biophys, 2017, 113(10): 2133-2142.
18
Nicholson C. Ion-selective microelectrodes and diffusion measurements as tools to explore the brain cell microenvironment [J]. Neurosci Methods, 1993, 48(3): 199-213.
19
Nicholson C, Tao L. Hindered diffusion of high molecular weight compounds in brain extracellular microenvironment measured with integrative optical imaging [J]. Biophys J, 1993, 65(6): 2277-2290.
20
Han H, Shi C, He Q, et al. A novel MRI tracer-based method for measuring water diffusion in the extracellular space of the rat brain [J]. IEEE J Biomed Health Inform, 2014, 18(3): 978-983.
21
Xu F, Han H, Fu Y, et al. Quantification of Gd-DTPA concentration in neuroimaging using T13D MP-RAGE sequence at 3.0 T [J]. Magn Reson Imaging, 2011, 29(6): 827-834.
22
Wang A, Wang R, Liu H, et al. The drainage of interstitial fluid in the deep brain is controlled by the integrity of myelination [J]. Aging Dis, 2019, 10(5): 937-948.
23
Steiner E, Enzmann GU, Zuber B, et al. Loss of astrocyte polarization upon transient focal brain ischemia as a possible mechanism to counteract early edema formation [J]. Glia, 2012, 60(11): 1646-1659.
24
Hrabetová S, Nicholson C. Dextran decreases extracellular tortuosity in thick-slice ischemia model [J]. J Cereb Blood Flow Metab, 2000, 20(9): 1306-1310.
25
Hrabetová S, Hrabe J, Nicholson C. Dead-space microdomains hinder extracellular diffusion in rat neocortex during ischemia [J]. J Neurosci, 2003, 23(23): 8351-8359.
26
Gaberel T, Gakuba C, Emery E, et al. Impaired glymphatic perfusion after strokes revealed by contrast-enhanced MRI: a new target for fibrinolysis? [J]. Stroke, 2014, 45(10): 3092-3096.
27
Baeten KM, Akassoglou K. Extracellular matrix and matrix receptors in blood-brain barrier formation and stroke [J]. Dev Neurobiol, 2011, 71(11): 1018-1039.
28
Adams RA, Schachtrup C, Davalos D, et al. Fibrinogen signal transduction as a mediator and therapeutic target in inflammation: lessons from multiple sclerosis [J]. Curr Med Chem, 2007, 14(27): 2925-2936.
29
Ryu JK, Davalos D, Akassoglou K. Fibrinogen signal transduction in the nervous system [J]. Thromb Haemost, 2009, 7Suppl 1(Suppl 1): 151-154.
30
Edwards DN, Bix GJ. Roles of blood-brain barrier integrins and extracellular matrix in stroke [J]. Am J Physiol Cell Physiol, 2019, 316(2): C252-C263.
31
Bobo RH, Laske DW, Oldfield EH, et al. Convection-enhanced delivery of macromolecules in the brain [J]. Proc Natl Acad Sci U S A, 1994, 91(6): 2076-2080.
32
Saito R, Tominaga T. Convection-enhanced delivery of therapeutics for malignant gliomas [J]. Neurol Med Chir (Tokyo), 2017, 57(1): 8-16.
33
Vogelbaum MA, Aghi MK. Convection-enhanced delivery for the treatment of glioblastoma [J]. Neuro Oncol, 2015, 17Suppl 2(Suppl 2): 3-8.
34
Mehta AM, Sonabend AM, Bruce JN. Convection-enhanced delivery [J]. Neurotherapeutics, 2017, 14(2): 358-371.
35
Han H, Xia Z, Li W, et al. Simple diffusion delivery via brain interstitial route for the treatment of cerebral ischemia [J]. Sci China Life Sci, 2011, 54(3): 235-239.
36
Xu F, Hongbin H, Xu W, et al. Greatly improved neuroprotective efficiency of citicoline by stereotactic delivery in treatment of ischemic injury [J]. Drug Deliv, 2011, 18(7): 461-467.
37
Fu Y, Li Y, Zhang W, et al. Bloodletting at Jing-well points decreases interstitial fluid flow in the thalamus of rats [J]. Tradit Chin Med, 2016, 36(1): 107-112.
[1] 王宏宇. 固定与活动平台假体在全膝关节置换术中的应用价值[J]. 中华关节外科杂志(电子版), 2023, 17(06): 871-876.
[2] 李善武, 叶永杰, 王兵, 王子呓, 银毅, 孙官军, 张大刚. 胫骨高位截骨与单髁置换的早期疗效比较[J]. 中华关节外科杂志(电子版), 2023, 17(06): 882-888.
[3] 彭旭, 邵永孚, 李铎, 邹瑞, 邢贞明. 结肠肝曲癌的诊断和外科治疗[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 108-110.
[4] 马伟强, 马斌林, 吴中语, 张莹. microRNA在三阴性乳腺癌进展中发挥的作用[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 111-114.
[5] 陈垚, 徐伯群, 高志慧. 改良式中间上入路根治术治疗甲状腺癌的有效性安全性研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 619-622.
[6] 杨瑞洲, 李国栋, 吴向阳. 腹股沟疝术后感染的治疗方法探讨[J]. 中华疝和腹壁外科杂志(电子版), 2023, 17(06): 715-719.
[7] 魏小勇. 原发性肝癌转化治疗焦点问题探讨[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 602-607.
[8] 张其坤, 商福超, 李琪, 栗光明, 王孟龙. 联合脾切除对肝癌合并门静脉高压症患者根治性切除术后的生存获益分析[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 613-618.
[9] 许丁伟, 马江云, 李新成, 黄洁. Alagille综合征疑诊为先天性胆道闭锁一例并文献复习[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 681-687.
[10] 崔佳琪, 吴迪, 陈海艳, 周惠敏, 顾元龙, 周光文, 杨军. TACE术后并发肝脓肿的临床诊治分析[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 688-693.
[11] 吴晨瑞, 廖锐, 贺强, 潘龙, 黄平, 曹洪祥, 赵益, 王永琛, 黄俊杰, 孙睿锐. MDT模式下肝动脉灌注化疗联合免疫靶向治疗肝细胞癌多处转移一例[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 713-716.
[12] 陆志峰, 周佳佳, 梁舒. 虚拟现实技术在治疗弱视中的临床应用研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(08): 891-895.
[13] 李田, 徐洪, 刘和亮. 尘肺病的相关研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(08): 900-905.
[14] 岳瑞雪, 孔令欣, 郝鑫, 杨进强, 韩猛, 崔国忠, 王建军, 张志生, 孔凡庭, 张维, 何文博, 李现桥, 周新平, 徐东宏, 胡崇珠. 乳腺癌HER2蛋白表达水平预测新辅助治疗疗效的真实世界研究[J]. 中华临床医师杂志(电子版), 2023, 17(07): 765-770.
[15] 符梅沙, 周玉华, 李慧, 薛春颜. 淋巴细胞免疫治疗对复发性流产患者外周血T淋巴细胞亚群分布与PD1/PD-L1表达的影响及意义[J]. 中华临床医师杂志(电子版), 2023, 17(06): 726-730.
阅读次数
全文


摘要