Fig 1.
Cisterna magna cannulation then intraperitoneal injection of the drug; wait half an hour and start MRI scanning. CM: cisterna magna, IP: intraperitoneal, ADC: apparent diffusion coefficient, and MRI: magnetic resonance imaging.
Fig 2.
Rat was placed in the prone position in a stereotaxic frame, using tooth and ear bars for stabilisation with the head fixed to 45° (snout). A 3 cm skin incision was made in the midline of the dorsal neck to expose the occipital crest and dural membrane covering the cisterna magna. A custom-made CM cannula (22-gauge, 2 mm Tip PEEK, SAI Infusion Technologies, RCMC-03) was advanced 2 mm into the subarachnoid space (i.e. CM space). CM: cisterna magna.
Fig 3.
Serial MRI images in the sagittal plane of a rat’s brain.
Using Gd-DTPA as the paramagnetic contrast agent reveals glymphatic transport with higher uptake and more parenchymal penetration over the whole brain over a period of two hours in the animals treated with the AQP4 facilitator (TGN-073) compared to vehicle-only treated rats. The time (in minutes) shows the change over time from starting the Gd-DTPA infusion.
Fig 4.
Averaged time activity curves (TAC) of three different regions of rats’ brains.
The percentage signal change is plotted as a function of time for theTGN-073 treated (n = 6, blue circles), vehicles (n = 6, orange circles), and artificial CSF (n = 3, grey circles) in (a) prefrontal cortex, (b) cerebellum and (c) whole brain. Pink shading on graphs indicates the period of tracer infusion. Shading on the anatomical images of the brain illustrates the location of ROIs, blue: prefrontal cortex, purple: cerebellum and orange: whole brain.
Fig 5.
Boxplots of apparent diffusion coefficient in the cerebral cortex (grey), the striatum (red), and whole brain (blue).
In each figure, left: TGN-073-treated group; right: vehicle group. Asterisks indicate significant differences: *P < 0.05.