Glymphatic Dysfunction in Migraine Mice Model

•Glymphatic flow dysfunction in mice with NTG-induced migraine.•Impaired expression and perivascular polarization of AQP4 in mice with NTG-induced migraine.•Further suppression of glymphatic function by TGN-020 aggravated the migraine pathological changes in mice. The glymphatic system is important for waste removal in the central nervous system. It removes soluble proteins and metabolic waste under the action of aquaporin-4 (AQP4) at the end of astrocytes. The glymphatic system plays a role in numerous neurological diseases; however, the relationship between migraine and the glymphatic system remains unclear. In this study, we explored the relationship between the glymphatic system and migraine using the nitroglycerin migraine model in C57/BL6mice. The glymphatic influx of cerebrospinal fluid tracer was reduced in mice in the migraine model, accompanied by decreased expression and impaired polarization of AQP4, thereby suggesting glymphatic dysfunction in migraine mice model. Then, further suppression of glymphatic function by TGN-020 (an AQP4 blocker) aggravated the migraine pathological changes in mice. The results indicated that glymphatic dysfunction may aggravate migraine pathology. Therefore, our findings revealed the potential role of the glymphatic system in migraine, providing possible targets for migraine prevention and treatment.