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2013 ; 11
(ä): 107
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Evaluating glymphatic pathway function utilizing clinically relevant intrathecal
infusion of CSF tracer
#MMPMID23635358
Yang L
; Kress BT
; Weber HJ
; Thiyagarajan M
; Wang B
; Deane R
; Benveniste H
; Iliff JJ
; Nedergaard M
J Transl Med
2013[May]; 11
(ä): 107
PMID23635358
show ga
BACKGROUND: Neurodegenerative diseases such as Alzheimer's are associated with
the aggregation of endogenous peptides and proteins that contribute to neuronal
dysfunction and loss. The glymphatic system, a brain-wide perivascular pathway
along which cerebrospinal fluid (CSF) and interstitial fluid (ISF) rapidly
exchange, has recently been identified as a key contributor to the clearance of
interstitial solutes from the brain, including amyloid ?. These findings suggest
that measuring changes in glymphatic pathway function may be an important
prognostic for evaluating neurodegenerative disease susceptibility or
progression. However, no clinically acceptable approach to evaluate glymphatic
pathway function in humans has yet been developed. METHODS: Time-sequenced ex
vivo fluorescence imaging of coronal rat and mouse brain slices was performed at
30-180 min following intrathecal infusion of CSF tracer (Texas Red- dextran-3, MW
3 kD; FITC- dextran-500, MW 500 kD) into the cisterna magna or lumbar spine.
Tracer influx into different brain regions (cortex, white matter, subcortical
structures, and hippocampus) in rat was quantified to map the movement of CSF
tracer following infusion along both routes, and to determine whether glymphatic
pathway function could be evaluated after lumbar intrathecal infusion. RESULTS:
Following lumbar intrathecal infusions, small molecular weight TR-d3 entered the
brain along perivascular pathways and exchanged broadly with the brain ISF,
consistent with the initial characterization of the glymphatic pathway in mice.
Large molecular weight FITC-d500 remained confined to the perivascular spaces.
Lumbar intrathecal infusions exhibited a reduced and delayed peak parenchymal
fluorescence intensity compared to intracisternal infusions. CONCLUSION: Lumbar
intrathecal contrast delivery is a clinically useful approach that could be used
in conjunction with dynamic contrast enhanced MRI nuclear imaging to assess
glymphatic pathway function in humans.