One of the most frequent forms of epilepsy in humans is temporal lobe epilepsy. Characteristic to this form of the disease is the frequent pharmacoresistance and the association with behavioural disorders and cognitive impairment. The objective of our study was to establish the degree of cognitive impairment in a rat model of temporal lobe epilepsy after an initial epileptogenic exposure but before of the onset of the effect of long-duration epilepsy.
Methods. For the experiment we used 11 rats. Status epilepticus was induced by systemic administration of a single dose of pilocarpine. The animals were continuously video-monitored to observe the occurrence of spontaneous recurrent seizures; during weeks 9-10 we performed eight-arm radial maze testing in order to assess the cognitive impairment.
Results. Animals developed spontaneous recurrent seizures after a 14-21 day latency with a daily average seizure density of 0.79±0.43 during weeks 9-10. Epileptic rats had significantly more working memory errors per session, more reference memory errors and the number of visited arms was also significantly higher. Accuracy was also lower in the pilocarpine treated group. Interestingly significant differences disappeared after six days of trials.
Conclusions. Our study shows behavioural deficits occurring after 9-10 weeks of epilepsy in the pilocarpine model of epilepsy applied to juvenile rats. In contrast to previous studies, we showed that juvenile rats with short duration of epilepsy are able to learn the behavioural task, therefore a morphopathological and/or behavioural “no-return point” regarding the development of severe cognitive impairment is not reached by status epilepticus alone.
Tag Archives: hippocampus
Cortical Epileptogenesis of Slowly Kindled Freely Moving Rats
Objective. Epilepsy is a neurological disorder that can be caused by many underlying pathologies. The epileptic and interictal manifestations that appear during the progression of chronic epilepsy are still not understood completely. One of the most frequent forms of this disease is temporal lobe epilepsy in which is clear involvement of the hippocampal formation. In order to study the electrografic progression of untreated seizures we used amygdala kindling in freely moving rats.
Methods. Seven animals were implanted with bilateral hippocampal and prefrontal electrodes. A bipolar electrode, implanted in the lateral nuclei of the left amygdala was used for stimulation. The kindled group of animals was stimulated daily with the minimum current intensity needed to reach the afterdischarge threshold. Behavioral changes during kindling were scored according to the Racine scale.
Results. The average seizure severity on the Racine scale was 2.6±0.4 by day 6 and 4.4±0.6 by day 20. The first spontaneous seizures appeared after 31 days of stimulation. During spontaneous seizures the preictal spike full width at half maximum increased gradually from 51±4msec to 110±5msec (p < 0.05) whereas the amplitude of the negative field potential deflection increased by 62% (p < 0.05).
|Conclusions. Our study showed that the progression of temporal lobe epilepsy, as seen in humans, can be reproduced in the kindling model with high fidelity. This study confirms in vivo the increase in preictal spike duration as well as the increase of the amplitude of negative field potential deflection during the preictal period.
Computer modeling of hippocampal CA1 pyramidal cells – a tool for in silico experiments
Objective. In silico experiments use mathematical models that capture as much as possible from the properties of the biological system under investigation. Our aim was to test the publicly available CA1 pyramidal cell models using the same simulation tasks, to compare them, and provide a systematic overview of their properties in order to improve the usefulness of these models as a tool for in silico experiments.
Methods. Parameters describing the morphology of the cells and the implemented biophysical mechanisms were collected from the ModelDB database of SenseLab Project. This data was analyzed in correlation with the purpose for which each particular model was developed. Multicompartmental simulations were run using the Neuron modeling platform. The properties of the action potentials generated in response to current injection, the firing pattern and the dendritic back-propagation were analyzed.
Results. The studied models were optimized to explore different physiological and pathological properties of the CA1 pyramidal cells. We could identify four broad classes of models focusing on: (i) initiation of the action potential, firing pattern and spike timing, (ii) dendritic back-propagation, (iii) dendritic integration of synaptic inputs and (iv) neuronal network activity. Despite the large variation of the active conductances implemented in the models, the properties of the individual action potentials were quite similar, but even the most complex models could not reproduce all studied biological phenomena.
Conclusions. At the moment the “perfect” pyramidal cell model is not yet available. Our work, hopefully, will help finding the best model for each scientific question under investigation.