TY  - JOUR
AU  - Mitlasóczki, Bence
AU  - Gutiérrez Gómez, Adrián
AU  - Kamali, Midia
AU  - Babushkina, Natalia
AU  - Baues, Mayan
AU  - Kück, Laura
AU  - Haubrich, André Nathan
AU  - Tamiolakis, Theodoros
AU  - Breuer, Annika
AU  - Granak, Simon
AU  - Schwering-Sohnrey, Merlin
AU  - Gerhauser, Ingo
AU  - Baumgärtner, Wolfgang
AU  - Schwarz, Martin Karl
AU  - Ewell, Laura
AU  - Opitz, Thoralf
AU  - Pitsch, Julika
AU  - Musall, Simon
AU  - Surges, Rainer
AU  - Mormann, Florian
AU  - Beck, Heinz
AU  - Wenzel, Michael
TI  - Hippocampal spreading depolarization as a driver of postictal ambulation.
JO  - Science translational medicine
VL  - 17
IS  - 816
SN  - 1946-6234
CY  - Washington, DC
PB  - AAAS
M1  - DZNE-2025-01436
SP  - eadv3260
PY  - 2025
AB  - Postseizure (postictal) symptoms are regularly encountered in epilepsy and can be life threatening, yet their neurobiological underpinnings remain understudied. Using two-photon or widefield imaging, field potential and unit recordings, optogenetics, and basic behavioral assessment under healthy conditions or viral encephalitis, we studied seizures and postictal symptoms in mice. We show a propensity of the hippocampus for seizure-associated spreading depolarization (sSD). Through optogenetic stimulation, we provide evidence that induced isolated hippocampal SD is sufficient to elicit postictal ambulation (PIA), whereas induced isolated seizure-like episodes are not. Furthermore, PIA occurred in the absence of SD progression to the neocortex. In addition, we analyzed Behnke-Fried depth-electrode recordings in four patients with focal epilepsy. Of 13 recorded seizures, we observed five slow shifts at seizure termination in the regionwise analysis that could reflect putative sSD. In support of our experiments in mice, we also found an increased vulnerability of the human temporomesial system (hippocampus and amygdala) for this phenomenon and longer recovery times of affected as compared with nonaffected brain regions. This work suggests sSD as a previously underrecognized pathoclinical entity underlying distinct postictal symptoms in epilepsy.
KW  - Animals
KW  - Hippocampus: physiopathology
KW  - Humans
KW  - Seizures: physiopathology
KW  - Male
KW  - Female
KW  - Walking: physiology
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Optogenetics
KW  - Electroencephalography
KW  - Adult
LB  - PUB:(DE-HGF)16
C6  - pmid:40961224
DO  - DOI:10.1126/scitranslmed.adv3260
UR  - https://pub.dzne.de/record/283024
ER  -