Analysis of Chronic Seizure Onsets after Intrahippocampal Kainic Acid Injection in Freely Moving Rats

Abstract

Summary:Purpose: The goal of this study was to analyze the transition period between interictal and ictal activity in freely moving rats with recurrent spontaneous seizures after unilateral intrahippocampal kainic acid (KA) injection.Methods: Pairs of tungsten electrodes (50 µm O/D) were implanted bilaterally under anesthesia at symmetrical points in the dentate gyrus (DG) and CA1 regions of anterior and posterior hippocampi and entorhinal cortex of adult Wistar rats. Stimulating electrodes were placed in the right angular bundle and KA was injected into the right posterior CA3 area of hippocampus after 1 week of baseline EEG recording. Beginning 24 h after injection, electrographic activity was recorded with video monitoring for seizures every day for 8 h/day for 60 days.Results: Seventy percent of seizures started locally in the DG ipsilateral to injection, with an increase in frequency of interictal EEG spikes (hypersynchronous type, HYP), and 26% of seizures started with a decrease of EEG amplitude with parallel increase in frequency (low-voltage fast type, LVF). During HYP seizures, a significant increase was observed in amplitude of beta-gamma range frequencies, ripple frequency, and fast ripple (FR) frequency, whereas during LVF seizure, an increase was noted only in the beta-gamma range. In all cases but one, an EEG wave preceded ripple and FR oscillations. Before seizure onset, the amplitude of DG-evoked responses to single pulses decreased, whereas the amplitude of the response to the second pulse delivered at 30-ms interval increased.Conclusions: If ripple and FR oscillations indicate the seizuregenerating neuronal substrate, these areas must be small and widespread, so that the probability of recording from them directly is very low. The decreased response to electrical stimulation before seizures could indicate a protective inhibitory mechanism that contains or prevents seizure occurrence. The presence of decreased paired-pulse suppression could indicate a network predisposition to follow an external input with a certain frequency.

Glutamatergic pre-ictal discharges emerge at the transition to seizure in human epilepsy

“…Ictal-like activity was not recorded from the dentate gyrus, CA3 region or entorhinal cortex although multi-unit activity in these areas was increased by the convulsants. Ictal-like field potentials were similar to intracranial EEG records of mesial temporal lobe seizures in humans 17,18 and animals 19 . In slices from 20 individuals they consisted of recurrent rhythmic bursts of frequency 3.7±0.1 Hz (95% CI: [3.6-3.7]).…”

“…6a left). A subset of pyramidal cells (7/39) increased firing in the 25 ms before the onset of PID field potentials (19±26 Hz, 95% CI: [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28], n=30 events from 3 cells; Fig. 6a right).…”

“…6b right). Effective interneuron firing frequency in the 25 ms before IID onset was 77±12 Hz (95% CI: [72-81], n=30 events from 3 cells) and 22±13 Hz (95% CI: [17][18][19][20][21][22][23][24][25][26][27], n=3 cells) in the 25 ms preceding PID. These data suggest that interneurons may be involved in IID initiation (6/6 interneurons fired before IID vs 0/39 pyramidal cells (Fisher's exact test, p<0.0001)).…”

Linking kindling to increased glutamate release in the dentate gyrus of the hippocampus through the STXBP5/tomosyn‐1 gene

“…Bragin, Azizyan, Almajano, Wilson, and Engel (2005) have shown low‐voltage fast‐onset (LVF) and hypersynchronous‐onset (HYP) spikes preceding spontaneous seizures in freely moving rats that had SE‐induced kainic acid hippocampal injections. Levesque, Salami, Gotman, and Avoli (2012) demonstrated LVF and HYP in the rat pilocarpine model of TLE.…”

Ictal and interictal high frequency oscillations in patients with focal epilepsy

“…Immediately preceding the seizure, inhibitory activity is reduced, which results in a reduction in spike activity, while the epileptogenic activity of the tissue increases, which results in an increase in HFOs. Then, at seizure onset, larger circuits get involved, appearing as rhythmic activity over more channels (Bragin et al, 2005(Bragin et al, , 2007Engel et al, 2009). Within these larger circuits the pathological tissue still oscillates at high frequencies, while in an adjacent but broader area spikes are seen.…”