Localized cortical injections of ethosuximide suppress spike-and-wave activity and reduce the resistance to kindling in genetic absence epilepsy rats (GAERS)

Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-α receptor activation in a genetic model of absence epilepsy

“…In literature, the only reported link between amygdala and absence epilepsy in humans, is an alteration in the amygdala volume in patients with childhood absence epilepsy (Schreibman Cohen et al, 2009). On the other side, absence animal models of epilepsy, such as WAG/Rij and GAERS rats, are resistant to amygdaloid kindling (Onat et al, 2007) and the demonstration that suppression of absence seizures by intracortical injection of ethosuximide reduces the resistance to kindling also supports a correlation between thalamo-cortical alterations and amygdala (Gülhan Aker et al, 2010). Furthermore, a not defined correlation between absence seizures and temporal lobe epilepsy has been previously demonstrated by injecting kainic acid into the amygdala of GAERS (Gurbanova et al, 2008).…”

The effect of amygdala kindling on neuronal firing patterns in the lateral thalamus in the GAERS model of absence epilepsy

“…A series of studies have demonstrated that the expression of SWDs in animal models of absence epilepsy results in resistance to the induction of experimental limbic epileptogenesis, in particular the secondary generalization of electrically kindled limbic seizures . The circuitries involved in the generation of limbic and absence seizures were previously thought to be distinct: Absence seizures occur as a result of hypersynchronized oscillations within the CTC loop, whereas temporal lobe seizures are associated with pathologic and electrophysiologic changes in the limbic structures including the amygdala, hippocampus, and entorhinal cortex .…”

“…The inhibition of low threshold T‐type calcium currents in thalamocortical network by the systemic or intracortical administration of the T‐type calcium channel blocker, ethosuximide, reduced the kindling resistance, with suppression of SWDs in adult GAERS . Furthermore, in young GAERS, because the CTC circuitry is immature, bilateral intracortical administration of ethosuximide completely abolished the kindling resistance …”

Tapping the Brakes: Cellular and Synaptic Mechanisms that Regulate Thalamic Oscillations

“…Injecting ethosuximide into the cortical focus but not adjacent cortical regions of Wag/rij and GAERS animals blocks spontaneous SWD (Manning et al, 2004; Aker et al, 2010), whereas thalamic ethosuximide infusion only partially blocks spontaneous SWD (Richards et al, 2003), which may reflect an undescribed I t -dependent cortical SWD generator or incomplete infusion into the target area. Ethosuximide’s well characterized reduction of I t and corresponding anti-oscillatory action in thalamus in vitro (Coulter et al, 1989b, 1989c; Huguenard and Prince, 1994a) suggest that systemic ethosuximide treatment blocks absence seizures at least in part by destabilizing thalamic output.…”

“…More thorough sampling within the apparent focal network of Wag/rij rats shows that similar oscillations occur first between cortical layer 6, which provides CT feedback, and the posterior thalamic nucleus, a higher order somatosensory TC relay (Lüttjohann and van Luijtelaar, 2012). Interestingly, targeted treatment of the focal cortical network is sufficient for seizure control, as ethosuximide infusion into the cortical focus (see below), but not adjacent cortical areas, rapidly blocks seizures in both Wag/rij and GAERS (Manning et al, 2004; Aker et al, 2010). It therefore appears that a restricted thalamocortical network initiates global SWDs; however, given the distributed nature of the network it is not feasible to rule out that an unsampled area might actually initiate the seizure.…”