Different phases of afterdischarge during rapid kindling procedure in mice

Abstract

SummaryThe basic mechanisms of hippocampal networks in epileptogenesis are not entirely understood. To help achieve a better understanding of these mechanisms, we studied the extra-cellular electricallyevoked responses in the hippocampi of mice during rapid kindling. Kindling protocol was achieved by stimulating the dorsal right hippocampus six times daily for four days using bipolar electrodes to produce sub-convulsive electrical discharges. Motor responses and analyzed electroencephalographic recordings showed progression from partial complex seizures to generalized seizures associated with different consecutive patterns within the afterdischarges. A spike-wave pattern appeared immediately after stimulation in combination with a poly-spike complex superimposed over the wave (AD1). AD1 was followed by a poly-spike complex (AD2), which was followed by a progressive modification of repetitive spikes (AD3). An ictal depression event was observed at the end of each AD3. Theta oscillations were observed at stage 1-2 of kindling, while beta/gamma oscillations appeared within AD2, associated with stage 4-5 from Racine's score. Benzodiazepine, a GABA (A) agonist (Diazepam) administered at non-sedative doses and only on days 3 and 4 of kindling, limited beta and gamma frequency bands and the progression of seizure severity, suggesting that the failure of GABA (A) agonism mediates the propagation or generalization of seizures. We conclude that different phases of afterdischarge occur during kindling and that high frequencies mediate generalization of seizures.

Platelet-activating factor receptor antagonism targets neuroinflammation in experimental epilepsy

“…As shown in previous studies, animals that reach stage 3–5 (Racine’s scale score) and obtain an AD duration of more than 25 s maintain a similar score and duration at least 1 week after subconvulsive hippocampal stimulation (Tu & Bazan, 2003; Musto et al., 2009). Therefore, in our studies, groups treated with the PAF antagonist, LAU‐0901 (2,4,6‐trimethyl‐1,4‐dihydro‐pyridine‐3,5‐dicarboxylic acid ester), or vehicle (2‐hydroxypropyl‐β‐cyclodextrin,1.4 mg/kg, i.p.…”

A new rapid kindling variant for induction of cortical epileptogenesis in freely moving rats

“…In our protocol, direct stimulation of the amygdaloid complex acts as the epileptogenic focus from where epileptic activity spreads toward projection areas that receive amygdala inputs, including hippocampal formation, which exhibited epilepsy-related cellular changes (Lothman et al, 1985; Ikegaya et al, 1996; Aronica et al, 2000; Valentine et al, 2004; Musto et al, 2009). Moreover, the progressive increase in the ADs duration showed that the use of stimulation intensities below the ADs threshold effectively promotes the long-term plasticity described in the kindling model (Racine, 1972a; Abe, 2001; Schubert et al, 2005) minimizing the cellular damage attributable to excessive electrical charge utilized in other protocols (Lothman et al, 1985, 1989; Von Bohlen und Halbach et al, 2004; Fournier et al, 2010).…”

Effects of neonatal hypoxic-ischemic episodes on late seizure outcomes in C57 black mice

“…Hippocampal stimulation was via a protocol modified from previous studies of fast kindling in mouse models (Smith et al, 2005;Musto et al, 2009;Ledri et al, 2012). Squared current pulses (durations of 0.5 ms) were generated from a Grass stimulator and delivered through an isolation unit (model S88H, Grass Medical Instruments, Warwick RI, USA).…”

“…hippocampus using a protocol adopted from previous studies of fast kindling in mouse models (Smith et al, 2005;Musto et al, 2009;Ledri et al, 2012). A train of high-frequency stimuli (60 Hz for 2 s, at the maximal intensity of 150 A) was applied every 10 min for up to 10 times until stage-5 motor seizures were evoked in individual mice.…”