A Pilot Study Evaluating the Effect of Artesunate on Glymphatic-Related Fluid Transport in Parkinson's Disease Mouse Models In Vivo and Ex Vivo.

AIMS: Artesunate (ART) has shown neuroprotective potential, but its effects on glymphatic-related fluid transport in Parkinson's disease (PD) remain unclear. This pilot study aimed to explore whether ART affects glymphatic-related fluid transport in a PD mouse model and to assess the feasibility of evaluating these changes in vivo.

METHODS

C57BL/6 WT and A53T mice (n = 6 each) were divided into four groups (WT, WT + ART, A53T, and A53T + ART) and treated with ART or DMSO for 7 days. Glymphatic-related fluid transport was assessed by dynamic MRI after intraventricular Gd-DTPA injection. Immunofluorescence evaluated α-syn, AQP4, and AQP4-GFAP colocalization, while transmission electron microscopy (TEM) assessed astrocytic end-feet integrity.

RESULTS

ART was associated with regionally heterogeneous changes in tracer-related MRI signal dynamics in both WT and A53T mice. In PD mice, ART was associated with partial restoration of AQP4 polarization in selected brain regions and improved perivascular astrocytic end-feet morphology, accompanied by reduced α-syn immunofluorescence signal in the substantia nigra.

CONCLUSION

ART was associated with regionally heterogeneous changes in glymphatic-related fluid transport dynamics and AQP4 polarization in this pilot PD mouse study. These preliminary findings support further investigation of ART as a potential modulator of brain fluid transport-related pathways in PD.