SPECT/CT imaging reveals CNS-wide modulation of glymphatic cerebrospinal fluid flow by systemic hypertonic saline
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
SPECT/CT imaging reveals CNS-wide modulation of glymphatic cerebrospinal fluid flow by systemic hypertonic saline. / Lilius, Tuomas O.; Rosenholm, Marko; Klinger, Laura; Mortensen, Kristian Nygaard; Sigurdsson, Björn; Mogensen, Frida Lind-Holm; Hauglund, Natalie L.; Nielsen, Malthe Skytte Nordentoft; Rantamaki, Tomi; Nedergaard, Maiken.
In: iScience, Vol. 25, No. 10, 105250, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - SPECT/CT imaging reveals CNS-wide modulation of glymphatic cerebrospinal fluid flow by systemic hypertonic saline
AU - Lilius, Tuomas O.
AU - Rosenholm, Marko
AU - Klinger, Laura
AU - Mortensen, Kristian Nygaard
AU - Sigurdsson, Björn
AU - Mogensen, Frida Lind-Holm
AU - Hauglund, Natalie L.
AU - Nielsen, Malthe Skytte Nordentoft
AU - Rantamaki, Tomi
AU - Nedergaard, Maiken
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - CENTRAL-NERVOUS-SYSTEM
KW - BLOOD-BRAIN-BARRIER
KW - RAT-BRAIN
KW - DELIVERY
KW - CLEARANCE
KW - PATHWAY
KW - TC-99M-DTPA
KW - TRANSPORT
U2 - 10.1016/j.isci.2022.105250
DO - 10.1016/j.isci.2022.105250
M3 - Journal article
C2 - 36274948
VL - 25
JO - iScience
JF - iScience
SN - 2589-0042
IS - 10
M1 - 105250
ER -
ID: 344645670