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Objective: The objective of the study was to propose a candidate animal model of absence status epilepticus induced by specific alpha-2a adrenergic receptor (α2AR) activation. We also aim to investigate the responsiveness of this model to classical anti-status or anti-absence medications., Methods: An α2AR agonist, dexmedetomidine (DEX), was injected intracerebroventricularly into adult rats with genetic absence epilepsy, and their electroencephalography (EEG) was recorded. The total duration, number, and mean duration of each spike-and-wave discharges (SWDs) were evaluated. The blocks of absence status events were classified as the initial and second sets of absence statuses. Ethosuximide (ETX) was administered as a pretreatment to another group of rats and later injected with 2.5 μg DEX. In addition, ETX, valproic acid (VPA), diazepam (DIAZ), and atipamezole (ATI) were administered after induced status-like events following DEX administration. Power spectral characteristics and coherence analysis were performed on the EEG to assess the absence status events and sleep., Results: The 2.5 μg dose of DEX increased the total SWD duration and induced continuous SWDs up to 26 min. Following the initial absence status event, sleep was induced; then, the second period of absence status-like activities were initiated. ETX pretreatment blocked the occurrence of absence status-like activities. Power spectral density analyses revealed that DEX-induced post-sleep activities had higher power in delta frequency band (1-4 Hz) and attenuated power of 7 Hz harmonics (14 and 21 Hz) than the pre-injection seizure. The mean duration of SWDs were decreased in all the groups, but occasional prolonged activities were seen in ETX or VPA-injected rats but not with DIAZ or ATI., Significance: This study presents an absence status epilepticus animal model that is activated by α2AR activation to investigate the pathophysiological role of absence status. Unlike other agents ATI switched off the second set of absence statuses to normal SWDs, without sedation or lethargy, can show it may preferentially block absence status-like activity., The Plain Language Summary: This study proposes a rat model for prolonged seizures, resembling absence status epilepticus. Activating the brain's alpha-2a adrenergic receptor with dexmedetomidine induced seizures lasting up to 26 minutes. Ethosuximide pretreatment and post-treatment with valproic acid, diazepam, and atipamezole decreased induced seizures. The findings suggest this model is valuable for studying absence status epilepticus. In addition, atipamezole normalized abnormal seizures without sedation, hinting at its potential for targeted treatment and further research., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Introduction: The genetic absence epilepsy rat from Strasbourg (GAERS) is a rat model for infantile absence epilepsy with spike-and-wave discharges (SWDs). This study aimed to investigate the potential of alpha 2A agonism to induce seizures during the pre-epileptic period in GAERS rats. Methods: Stereotaxic surgery was performed on male pups and adult GAERS rats to implant recording electrodes in the frontoparietal cortices (right/left) under anesthesia (PN23-26). Following the recovery period, pup GAERS rats were subjected to electroencephalography (EEG) recordings for 2h. Before the injections, pup epileptiform activity was examined using baseline EEG data. Dexmedetomidine was acutely administered at 0.6 mg/kg to pup GAERS rats 2-3 days after the surgery and once during the post-natal (PN) days 25-29. Epileptiform activities before injections triggered unilateral SWDs and induced sleep durations, and power spectral density was evaluated based on EEG traces. Results: The most prominent finding of this study is that unilateral SWD-like activities were induced in 47% of the animals with the intraperitoneal dexmedetomidine injection. The baseline EEGs of pup GAERS rats had no SWDs as expected since they are in the pre-epileptic period but showed low-amplitude non-rhythmic epileptiform activity. There was no difference in the duration of epileptiform activities between the basal EEG groups and DEX-injected unilateral SWD-like-exhibiting and non-SWD-like activities groups; however, the sleep duration of the unilateral SWD-like-exhibiting group was shorter. Power spectrum density (PSD) results revealed that the 1.75-Hz power in the left hemisphere peaks significantly higher than in the right. Discussion: As anticipated, pup GAERS rats in the pre-epileptic stage showed no SWDs. Nevertheless, they exhibited sporadic epileptiform activities. Specifically, dexmedetomidine induced SWD-like activities solely within the left hemisphere. These observations imply that absence seizures might originate unilaterally in the left cortex due to α2AAR agonism. Additional research is necessary to explore the precise cortical focal point of this activity. [ABSTRACT FROM AUTHOR]

Objective: Dexmedetomidine induces a two-phase of events: an initial period of absence status-like activity followed by sleep, then an immediate switch from sleep to the second period of absence status-like events (Yavuz et al, 2022). We aim to explore the effects of the de-activation of 2AR by atipamezole on these state transitions induced by dexmedetomidine in Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Methods: Specific a2AR agonist, dexmedetomidine (2.5 µg), was administered via intracerebroventricular injection to adult GAERS (n=8) to induce absence status-like events. When the initial absence status-like events were triggered, atipamezole (1 mg/kg) was injected intraperitoneally. Electroencephalography (EEG) recordings were obtained 30 min before the initial administration of dexmedetomidine and 2 hours after atipamezole. The duration of SWDs and prolonged SWDs; we defined as absence status-like activities and the anesthesia sleep between were analyzed. Results: Following dexmedetomidine injection in adult GAERS, initial absence status-like activity with duration of 128±13.74 min that abruptly converts to a sleep-anesthesia was triggered. When the 31.43±2.53 long sleep anesthesia was over, it abruptly switched to prolonged chain of SWDs in 100% of the animals. Atipamezole suppressed the prolonged seizure activities for 120 min and no activity above 1 min has been observed in the EEGs (p<0.01). SWDs with a duration of 10-16 sec still occurred with atipamezole. The mean duration at the 140th min of SWDs with atipamezole (15.2±3.8; n=4) was similar to the control groups of naïve GAERS: (14.2±1.8; n=4), which SWDs are expressed spontaneously. Conclusion: Activation of a2AR triggered a switch mechanism between prolonged SWDs, anesthesia sleep, and subsequent return to SWDs, but atipamezole recovered sleep activity as expected as well as absence status by removing two phase of events. This finding provides evidence that a2AR receptor targets may be the switch mechanism between the sleep and SWDs. [ABSTRACT FROM AUTHOR]