SPECT/CT imaging reveals CNS-wide modulation of glymphatic cerebrospinal fluid flow by systemic hypertonic saline
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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 (99)mTc-diethylenetriaminepen-taacetic acid (DTPA) administered through intracisternal, intrastriatal, or intravenous route in anesthetized rats. Co-administration of systemic HTS increased intracranial exposure to intracisternal (99)mTc-DTPA by similar to 80% during imaging. In contrast, HTS had minimal effects on brain clearance of intrastriatal (99)mTc-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.
Original language | English |
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Article number | 105250 |
Journal | iScience |
Volume | 25 |
Issue number | 10 |
Number of pages | 17 |
ISSN | 2589-0042 |
DOIs | |
Publication status | Published - 2022 |
- CENTRAL-NERVOUS-SYSTEM, BLOOD-BRAIN-BARRIER, RAT-BRAIN, DELIVERY, CLEARANCE, PATHWAY, TC-99M-DTPA, TRANSPORT
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