Fig. 1.

Chronic pharmacological blockade of AQP4 results in sustained glymphatic inhibition. A Representative example of whole brain images with psuedocoloured fluorescence overlaid, illustrating the dramatic reduction of brain surface coverage of fluorescence tracer (TxR-d3, 3 kDa) following chronic treatment with TGN-020 (50 mg/kg) compared to vehicle. Quantification of this signal B shows that in all three orientations, TGN-020 treated mice exhibit a reduction in tracer coverage. Sectioning of brains and imaging by fluorescence microscopy demonstrated a similar difference; C representative examples of a brain section (~ 1 mm lateral to the midline) of a vehicle treated and a TGN-020 treated mouse brain, showing clear surface penetration of TxR-d3 in the vehicle treated but not TGN-020 treated animal. D Quantification of the % area of each section covered by the tracer demonstrates this difference more clearly (shaded area indicates SEM of animals examined). E Area under curve of data shown in (D). *=p < 0.05, **=p < 0.01, n = 3–4 per group