Enhancing glymphatic fluid transport by pan-adrenergic inhibition suppresses epileptogenesis in male mice

Qian Sun, Sisi Peng, Qiwu Xu, Pia Weikop, Rashad Hussain, Wei Song, Maiken Nedergaard () and Fengfei Ding ()
Additional contact information
Qian Sun: University of Rochester
Sisi Peng: University of Rochester
Qiwu Xu: University of Rochester
Pia Weikop: University of Copenhagen Faculty of Health and Medical Sciences
Rashad Hussain: University of Rochester
Wei Song: University of Rochester
Maiken Nedergaard: University of Rochester
Fengfei Ding: University of Rochester

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Epileptogenesis is the process whereby the previously normally functioning brain begins to generate spontaneous, unprovoked seizures. Status epilepticus (SE), which entails a massive release of neuronal glutamate and other neuroactive substances, is one of the best-known triggers of epileptogenesis. We here asked whether pharmacologically promoting glymphatic clearance during or after SE is beneficial and able to attenuate the subsequent epileptogenesis. We induced SE in adult male mice by intrahippocampal kainic acid (KA) infusion. Acute administration of a cocktail of adrenergic receptor antagonists (propranolol, prazosin, and atipamezole: PPA), enhanced glymphatic flow and effectively reduced the severity of spontaneous seizures in the chronic phase. The PPA treatment also reduced reactive gliosis and inhibited the loss of polarized expression of AQP4 water channels in the vascular endfeet of astrocytes. Administration of PPA after cessation of SE (30 hours post KA) also effectively suppressed epileptogenesis and improved outcome. Conversely, mice with constitutively low glymphatic transport due to genetic deletion of the aquaporin 4 (AQP4) water channel showed exacerbation of KA-induced epileptogenesis. We conclude that the pharmacological modulation of glymphatic fluid transport may represent a potential strategy to dampen epileptogenesis and the occurrence of spontaneous seizures following KA-induced SE.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53430-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53430-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53430-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().