Authors :
Presenting Author: Hana Kubova, PharmD, PhD, DSc – Institute of Physiology CAS
Pavel Mares, Prof., MUDr, PhD, DSc – Institute of Physiology CAS
Alika Chernova, BS – Institute of Physiology CAS
Grigoriy Tsenov, PhD – Institute of Physiology CAS
Anna Mikulecka, RNDr, PhD – Institute of Physiology CAS
Andrea Grigelova, MSc. – Institute of Physiology CAS
Rationale:
Seizures in neonates are associated with a high risk for subsequent epilepsy and adverse neurodevelopmental consequences. In the present study, we focused on immediate functional consequences of recurrent seizures induced with flurothyl (FLU) in neonatal rats. Our study aimed to find out whether acquired seizures are followed by (1) the development of spontaneous seizures and (2) early impairment of cognitive and social functions. Methods:
Starting at postnatal day 6 (P6), Wistar rats of both sexes were exposed to FLU-induced generalized tonic-clonic seizures (5 seizures/day) for five consecutive days. Following FLU exposure, animals were implanted with epidural cortical electrodes at P12, 15 and 25 (n = 8 in both C and FLU groups) and after a short rest video/EEG monitored for 4 hours for presence of spontaneous seizures (SRS). The incidence and number of electrographic seizures (frequency 5-9 Hz, duration >5s) were assessed in both controls and FLU-exposed animals. Additional groups of animals (n=10 per sex and treatment group) were exposed to the homing response test at P18 and the huddling test at P12 and P14, with ultrasound vocalization of the separated pup recorded during the homing response test.
Results:
SRS were observed in all P12 and P15 animals exposed to FLU. At P12, the average seizure number per observation period was 15±12 in females and 13±5 in males. At P15, the average seizure number per observation period was n=10±7 and n=18±6, respectively. At P25, SRS were observed in 8% of females and 31% of males. In controls, 1 or 2 seizures were observed in P12 and P15 in 1 animal per age and sex group. In the homing response test, FLU-exposed animals of both sexes frequently failed to reach the target zone, unlike controls, who were 100% successful. FLU-exposed animals also showed more frequent ultrasonic vocalizations when failing this test. In the huddling test, FLU-exposed animals of both sexes often stayed separated or left the huddle, particularly before displaying seizure-related behaviors. All P12 animals leaving the huddle exhibited motor clonic seizures. At P14, FLU-exposed animals still showed a tendency to stay separated from the huddle, though motor seizures were less pronounced compared to the younger group.Conclusions:
Our data show spontaneous seizures enduring after the end of FLU-exposure. The impairments observed in the homing response and huddling tests indicate that early-life seizures lead to early disruptions in cognitive and social functions. These findings reveal the immediate and impacts of neonatal seizures on development, emphasizing the need for further investigation into the long-term effects of early life seizures on cognitive and social development.
Funding:
Supported by grant 23-05274S of the Czech Science Foundation, project National Institute for Neurological Research (Programme EXCELES, ID Project No. LX22NPO5107) (co-supported by EU) and Research Project RVO 67985823.