SPECT/CT imaging reveals CNS-wide modulation of glymphatic cerebrospinal fluid flow by systemic hypertonic saline.

Autor:	Lilius TO; Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Department of Emergency Medicine and Services, Helsinki University Hospital and University of Helsinki, Helsinki, Finland., Rosenholm M; Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Klinger L; Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Mortensen KN; Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Sigurdsson B; Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Mogensen FL; Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Neuro-immunology Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg.; Doctoral School of Science and Technology, University of Luxembourg, Esch-sur-Alzette, Luxembourg., Hauglund NL; Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Nielsen MSN; Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Rantamäki T; Laboratory of Neurotherapeutics, Doctoral Program in Drug Research, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.; SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Nedergaard M; Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, 601 Elmwood Avenue, Box 645, Rochester, NY 14642, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2022 Sep 29; Vol. 25 (10), pp. 105250. Date of Electronic Publication: 2022 Sep 29 (Print Publication: 2022).
DOI:	10.1016/j.isci.2022.105250
Abstrakt:	Intrathecal administration enables central nervous system delivery of drugs that do not bypass the blood-brain barrier. Systemic administration of hypertonic saline (HTS) enhances delivery of intrathecal therapeutics into the neuropil, but its effect on solute clearance from the brain remains unknown. Here, we developed a dynamic in vivo single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging platform to study the effects of HTS on whole-body distribution of the radiolabeled tracer 99m Tc-diethylenetriaminepentaacetic acid (DTPA) administered through intracisternal, intrastriatal, or intravenous route in anesthetized rats. Co-administration of systemic HTS increased intracranial exposure to intracisternal 99m Tc-DTPA by ∼80% during imaging. In contrast, HTS had minimal effects on brain clearance of intrastriatal 99m Tc-DTPA. In sum, SPECT/CT imaging presents a valuable approach to study glymphatic drug delivery. Using this methodology, we show that systemic HTS increases intracranial availability of cerebrospinal fluid-administered tracer, but has marginal effects on brain clearance, thus substantiating a simple, yet effective strategy for enhancing intrathecal drug delivery to the brain. Competing Interests: The authors declare no competing interests. (© 2022 The Authors.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu