Orexin Receptor Antagonism Improves Sleep and Reduces Seizures inKcna1-null Mice

Abstract

Dual orexin receptor antagonists may be an effective sleeping aid in epilepsy, and warrants further study on their somnogenic and ant-seizure effects in other epilepsy models.

Regulation of brain PPARgamma2 contributes to ketogenic diet anti-seizure efficacy

“…The Kv1.1KO mouse is a model of temporal lobe epilepsy that exhibits severe and frequent spontaneous recurrent seizures (SRS) (Simeone et al, 2013, 2014a,b; Fenoglio-Simeone et al, 2009a,b Kim et al, 2015; Roundtree et al, 2016). We have previously demonstrated that the KD is highly efficacious in Kv1.1KO mice attenuating seizures by 70–80% (Fenoglio-Simeone et al, 2009a; Kim et al, 2015).…”

“…Seizure frequency was quantified and further weighted for Racine scale severity to calculate a seizure burden index score for each mouse. A seizure burden index score provides an important consolidated metric to convey the effect of a given treatment on both the frequency and severity of seizures (Simeone et al 2014a; Barker-Haliski et al, 2015; Roundtree et al, 2016). Similar to our previous findings (Fenoglio-Simeone et al, 2009a,b Kim et al, 2015), KD treatment decreased seizure frequency and burden of Kv1.1KO mice by ~70% (Fig.4).…”

“…One ground (1.5mm anterior lamba, 1.5mm lateral) and two subdural (1mm posterior Bregma, 1.5mm bilateral) iEEG electrodes were implanted, secured and attached to a headmount. Following a 5–6 day recovery, seizures were monitored for forty-eight hours using a continuous infrared video surveillance system time-synced to an EEG recording system (Pinnacle Technology, Inc., Lawrence, KS, U.S.A) as we have described (Roundtree et al, 2016; Simeone et al, 2014a; Fenoglio-Simeone et al, 2009a,b). EEG recordings were acquired with a 250 Hz sampling rate and band-pass filtered between 0.5 and 40 Hz.…”

“…Seizure severity was scored using a modified Racine scale: 0-normal; 1-myoclonic jerk; 2-side-to-side head movement; 3-forelimb/hindlimb clonus, tail extension, a single rearing event; 4-continuous rearing and falling; 5-severe tonic-clonic seizures. To weigh the incidence and severity of seizures, seizure burden index (SBI) scores were calculated using the equation: SBI = [Σ(σ i γ i )]/ε, where σ indicates the severity; i indicates each stage of seizure (1–5); γ is the frequency; and ε indicates the total number of epochs scored as we have described (Simeone et al, 2014a; Roundtree et al, 2016; Simeone et al, 2016). …”

Respiratory dysfunction progresses with age in Kcna1‐null mice, a model of sudden unexpected death in epilepsy

“…For example, a buildup of CO 2 in the lungs will elevate blood CO 2 levels to signal peripheral and central chemoreceptors to increase respiration rate, which in turn stabilizes blood gasses. 38 Therefore, increased orexin neuronal activation may be a central driver of increased respiratory responses of Kcna1 À/À mice. Respiratory drive reflects the volume of air that enters and exits the lungs in one cycle normalized to inspiration time.…”