Analysis of chronic seizure onsets after intrahippocampal kainic acid injection in freely moving rats.
OBJECTIVE
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 microm 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 seizure-generating 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.
Bragin
Anatol
A
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. abragin@ucla.edu
Azizyan
Avetis
A
Almajano
Joyel
J
Wilson
Charles L
CL
Engel
Jerome
J
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D003344:Cortical Synchronization / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects* / Q000706:statistics & numerical data*; D018728:Entorhinal Cortex / Q000187:drug effects / Q000503:physiopathology; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D007608:Kainic Acid / Q000494:pharmacology*; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D007608:Kainic Acid