Izvestiya of Saratov University.

Chemistry. Biology. Ecology

ISSN 1816-9775 (Print)
ISSN 2541-8971 (Online)
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Language: 
Russian
Heading: 
Biology
Article type: 
Article
UDC: 
612.825
DOI: 
10.18500/1816-9775-2020-20-3-339-351

The Study of Lymphatic Draina ge Function of the Brain After Opening the Blood-Brain Barrier and During Drugged Sleep

Autors: 
Zinchenko Ekaterina M., Saratov State University
Klimova Maria M., Saratov State University
Khorovodov Aleksandr P., Saratov State University
Agranovich Ilana M., Saratov State University
Esma Sharif Ali, Saratov State University
Terskov Andrey V., Saratov State University
Dubrovsky Alexander I., Saratov State University
Shirokov Aleksandr A., Institute of Biochemistry and Physiology of Plants and Microorganisms of the Russian Academy of Sciences - Subdivision of the Federal State Budgetary Research Institution Saratov Federal Scientific Centre of the Russian Academy of Sciences (IBPPM RAS)
Mamedova Aysel T., Saratov State University
Blohina Inna A., Saratov State University
Lezhnev Nikita D., Saratov State University
Romashchenko Alexander V., Institute of Cytology and Genetics SB RAS
Tuchin Valeriy V., Saratov State University
Semyachkina-Glushkovskaya Oksana V., Saratov State University
Abstract: 

In studies on male adult rats, the activation of the functions of the lymphatic system of the brain (LSM) was studied during drugged sleep and after the opening of the blood-brain barrier (BBB) by sound. The cleaning and drainage functions of LSM were studied by removing contrast agents from the brain in real time using magnetic resonance imaging (MRI) and optical coherence tomography (OCT). It was found that the opening of the BBB is accompanied by an immediate activation of the lymphatic drainage function of the brain, which is manifested in a faster elimination of gadolinium (MRI data) and gold nanorods (OCT results) from its tissues. For the first time, it was revealed that drug sleep and the opening of BBB have similar dynamics of changes in patterns reflected in the electrical activity of the brain. The results are pioneering and open up new physiological patterns in the study of the functions of LSM, which contribute to the appearance of innovative strategies in the development of breakthrough technologies in therapeutic modulations of the lymphatic drainage processes of the brain.

Key words: 
cerebral lymphatic system
blood-brain barrier
magnetic resonance imaging
electroencephalography
optical coherence tomography
rats
Reference: 
  1. Gildner Th., Salinas-Rodriguez A., Manrique-Espinoza B., Moreno-Tamayo K., Kowal P. Does poor sleep impair cognition during aging? Longitudinal associations between changes in sleep duration and cognitive performance among older Mexican adults // Arch. Gerontol. Geriatr. 2019. Vol. 83. P. 161–168. DOI: https://doi.org/10.1016/j.archger.2019.04.014
  2. Lin J., Li F. D., Chen X. G., He F., Zhai Y. J., Pan X. Q., Wang X. Y., Zhang T., Yu M. Association of postlunch napping duration and night-time sleep duration with cognitive impairment in Chinese elderly : a cross-sectional study // BMJ Open. 2018. Vol. 12. P. e023188. DOI: https://doi.org/10.1136/bmjopen-2018-023188
  3. Rechtschaffen A., Bergmann B. M. Sleep deprivation in the rat by the disk-over-water method // Behav. Brain. Res. 1995. Vol. 69. P. 55–63. DOI: https://doi.org/10.1016/0166- 4328(95)00020-T
  4. Da Mesquita S., Louveau A., Vaccari A., Smirnov I., Cornelison R. C., Kingsmore K. M., Contarino C., OnengutGumuscu S., Farber E., Raper D., Viar K. E., Powell R. D., Baker W., Dabhi N., Bai R., Cao R., Hu S., Rich S. S., Munson J. M., Lopes M. B., Overall C. C., Acton S. T., Kipnis J. Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease // Nature. 2018. Vol. 560, № 7717. P. 185. DOI: https://doi.org/10.1038/s41586-018-0689-7
  5. Zinchenko E., Navolokin N., Shirokov A., Khlebtsov B., Dubrovsky A., Saranceva E., Abdurashitov A., Khorovodov A., Terskov A., Mamedova A., Klimova M., Agranovich I., Martinov D., Tuchin V., Semyachkina-Glushkovskaya O., Kurts J. Pilot study of transcranial photobiomodulation of lymphatic clearance of beta-amyloid from the mouse brain: breakthrough strategies for nonpharmacologic therapy of Alzheimer’s disease // Biomed. Opt. Express. 2019. Vol. 10. P. 4003–4017. DOI: https://doi.org/10.1364/BOE.10.004003
  6. Semyachkina-Glushkovskaya O., Chehonin V., Borisova E., Fedosov I., Namykin A., Abdurashitov A., Shirokov A., Khlebtsov B., Lyubun Y., Navolokin N., Ulanova M., Shushunova N., Khorovodov A., Agranovich I., Bodrova A., Sagatova M., Shareef A. E., Saranceva E., Iskra T., Dvoryatkina M., Zhinchenko E., Sindeeva O., Tuchin V., Kurths J. Photodynamic opening of the blood-brain barrier and pathways of brain clearing // J. Biophotonics. 2018. Vol. 11. P. e201700287. DOI: https://doi.org/10.1002/jbio.201700287
  7. Semyachkina-Glushkovskaya O., Abdurashitov A., Dubrovsky A., Bragin D., Bragina O., Shushunova N., Maslyakova G., Navolokin N., Bucharskaya A., Tuchin V., Kurths J., Shirokov A. Application of optical coherence tomography for in vivo monitoring of the meningeal lymphatic vessels during opening of blood-brain barrier: mechanisms of brain clearing // J. Biomed. Opt. 2017. Vol. 22. P. 121719. DOI: https://doi.org/10.1117/1.JBO.22.12.121719
  8. Semyachkina-Glushkovskaya O., Postnov D., Kurths J. Blood-brain barrier, lymphatic clearance, and recovery: Ariadne’s thread in labyrinths of hypotheses // Int. J. Mol. Sci. 2018. Vol. 19, № 12. P. 3818. DOI: https://doi.org/10.3390/ ijms19123818
  9. Achariyar T., Li B., Peng W., Verghese P. B., Shi Y., McConnell E., Benraiss A., Kasper T., Song W., Takano T., Holtzman D.M., Nedergaard M., Deane R. Glymphatic distribution of CSF-derived apoE into brain is isoform specifi c and suppressed during sleep deprivation // Mol. Neurodegener. 2016. Vol. 11, № 1. P. 74. DOI: https://doi.org/10.1186/s13024-016-0138-8
  10. Robinson. R. When it comes to glymphatic clearance, not all anesthetics, or sleep stages, are equal // Neurology today. 2019. Vol. 19, № 7. P. 1–15. DOI: https://doi.org/10.1097/01.NT.0000557712.74473.83
  11. Hablitz L. M., Vinitsky H. S., Sun Q., St?ger F. F., Sigurdsson B., Mortensen K. N., Lilius T. O., Nedergaard M. Increased glymphatic infl ux is correlated with high EEG delta power and low heart rate in mice under anesthesia // Sci. Adv. 2019. Vol. 5, № 2. P. eaav5447. DOI: https://doi.org/10.1126/sciadv.aav5447
  12. Benveniste H. Glymphatic System Function in Relation to Anesthesia and Sleep States // Anesth. Analg. 2019. Vol. 128, № 4. P. 747–758. DOI: https://doi.org/10.1213/ANE.0000000000004069
  13. Semyachkina-Glushkovskaya O., Chekhonin V., Bragin D., Bragina O., Vodovozova E., Alekseeva A., Salmin V., Morgun A., Malinovskaya N., Osipova E., Boytsova E., Tohidpour A., Shirokov A., Navolokin N., Yang Y., Zhang C., Feng W., Abdurashitov A., Ulanova M., Shushunova N., Khorovodov A., Terskov A., Esmat Shareef A., Pavlov A., Luo Q., Zhu D., Tuchin V., Kurths J. Loud music and the specific sound stress open the blood-brain barrier: new fundamental, biomedical, and social aspects // bioRxiv. 2018. URL: https://www.biorxiv.org/content/10.1101/509042v1.article-info. DOI: https://doi.org/10.1101/509042 (дата обращения: 01.03.2020).
  14. Qi Y., Yu T., Xu J., Wan P., Ma Y., Zhu J., Li Y., Gong H., Luo Q., Zhu D. FDISCO: Advanced solvent-based clearing method for imaging whole organs // Sci. Adv. 2019. Vol. 5, № 1. P. eaau8355. DOI: https://doi.org/10.1126/sciadv.aau8355
  15. Wang H. L., Lai T. W. Optimization of Evans bl ue quantitation i n limited rat tissue s amples // Sci. Rep. 2014. Vol. 4. P. 6588. DOI: https://doi.org/10.1038/srep06588
  16. Bragin D., Kameneva M., Bragina O., Thomson S., Statom G., Lara D., Yang Y., Nemoto E. Rheological effects of drag-reducing polymers improve cerebral blood fl ow and oxygenation after traumatic brain injury in rats // J. Cereb. Blood Flow Metab. 2017. Vol. 37, № 3. P. 762–775. DOI: https://doi.org/10.1007/978-3-319-91287-5_7
  17. Patlak C. S., Blasberg R. G., Fenstermacher J. D. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data // J. Cereb. Blood Flow Metab. 1983. Vol. 3, № 1. P. 1–7. DOI: https://doi.org/10.1038 / jcbfm.1983.1
  18. Ewing J., Knight R. A., Nagaraja T. N., Yee J. S., Nagesh V., Whitton P.A., Li L., Fenstermacher J. D. Patlak plots of Gd-DTPA MRI data yield bloo d-brain transfer constants concordant with those of 14C – sucrose in areas of bloodbrain opening // Magn. Reson. Med. 2003. Vol. 50, № 2. P. 283–292. DOI: https://doi.org/10.1002/mrm.10524
  19. Khlebtsov B., Khanadeev V., Sukhorukov G., Khlebtsov N. Overgrowth of gold nanorods by using a binary surfactant mixture // Langmuir. 2014. Vol. 30, № 6. P. 1696–1703. DOI: https://doi.org/10.1021/la404399n
  20. Louveau A., Smirnov I., Keyes T. J., Eccles J. D., Rouhani S. J., Peske J. D., Derecki N. C., Castle D., Mandell J. W., Lee K. S., Harris T. H., Kipnis J. Structural and functional features of central nervous system lymphatic vessels // Nature. 2015. Vol. 523, № 7560. P. 337. DOI: https://doi.org/10.1038/nature14432
  21. Aspelund A., Antila S., Proulx S. T., Karlsen T. V., Karaman S., Detmar M., Wiig H., Alitalo K. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules // J. Exp. Med. 2015. Vol. 212, № 7. P. 991–999. DOI: https://doi.org/10.1084/jem.20142290
  22. Xie L., Kang H., Xu Q., Chen M. J., Liao Y., Thiyagaraja M., O’Donnell J., Christensen D. J., Nicholson C., Iliff J. J. Sleep drives metabolite clearance from the adult brain // Science. 2013. Vol. 342. P. 373–377. DOI: https://doi.org/10.1126/science.1241224
  23. Fultz N. E., Bonmassar G., Setsompop K., Stickgold R. A., Rosen B. R., Polimeni J. R., Lewis L. D. Coupled electrophysiological, hemodynamic, and cerebrospinal fl uid oscillations in human sleep // Science. 2019. Vol. 366. P. 628–663. DOI: https://doi.org/10.1126/science.aax5440
Received: 
31.08.2020