Cortical spreading depolarisation impacts glymphatic flow, with consequences for migraine aura

Cortical spreading depolarisation, which is involved as a pathophysiological substrate in migraine aura, was found to alter glymphatic flow in a mouse model study.

Ms Zi-Rou Jiang (National Yang Ming Chiao Tung University, Taiwan) and colleagues designed a study in mice to determine the role of glymphatics in cortical spreading depolarisation [1]. The cortical spreading depolarisation events were induced with potassium chloride or an optogenetic method before and after cerebrospinal fluid tracer injection. Glymphatic dynamics were assessed using macroscopic imaging, while glymphatic clearance was assessed by monitoring the tracer transitioning into the deep cervical lymph node.

“The cerebrospinal fluid tracer signal was always larger on the contralateral side than on the ipsilateral side,” said Ms Jiang. “We also saw that at the moment of cortical spreading depolarisation induction, the cerebrospinal fluid tracer signal showed a rapid and abundant influx in the ipsilateral side.” The cerebrospinal fluid tracer signal was found to be significantly increased in the ipsilateral side at all timepoints assessed following cortical spreading depolarisation (at 30, 60, 90, and 120 minutes). Finally, drainage of the cerebrospinal fluid was also assessed with the tracer, showing that fluorescence decreased in the ipsilateral compared with contralateral deep cervical lymph node after spreading depolarisation induction, “potentially altering glymphatic function,” added Ms Jiang.

“In conclusion, our study indicated that optogenetically-induced spreading depolarisation evokes rapid influx but delayed clearance of the glymphatic flow,” said Ms Jiang. “We clearly saw a difference between the control group and the cortical spreading depolarisation group, potentially indicating that a cortical spreading depolarisation event can alter glymphatic function, not only in the efflux but also in the influx.”

1. Jiang Z, et al. Optogenetically-induced spreading depolarization evokes rapid influx but delayed clearance of the glymphatic flow. 18^th European Headache Congress, 4–7 December 2024, Rotterdam, the Netherlands.

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Posted on 6 January 20256 January 2025