The Relevance of Kindling for Human Epilepsy

Abstract

Summary:Kindling is one of the most widely used models of seizures and epilepsy, and it has been used in its more than three decade history to provide many key insights into seizures and epilepsy. It remains a mainstay of epilepsy related research, but the question remains how the results from kindling experiments further our understanding of the underlying neurobiology of human epilepsy. In this article we compare the basic features of kindling and human epilepsy, especially human limbic or temporal lobe epilepsy. In this review we focus on a limited number of topics that may show areas in which kindling has been often cited as a tool for better understanding of human epilepsy. These areas include the underlying circuits, the importance of seizure spontaneity, the associated neuropathology, the contribution of genetics, seizure susceptibility, and the underlying pathophysiology of epilepsy. In the course of this article we will show that there are many features that kindling can teach us by direct comparison or implication about human temporal epilepsy. We will also see that not all findings associated with kindling may be applicable to the human condition. Ultimately we wish to encourage critical thinking about kindling and the similarities that it shares and does not share with the human epilepsy so the results from studies using this model are applied rationally to further our insights the mechanisms of human epilepsy. Key Words: Kindling-Epilepsy-Animal models of human disease.This first paragraph is a disclaimer. One should be wary of articles and authors that start with disclaimers. What follows is a very personal view of kindling and what it can teach us about human epilepsy. The article starts philosophically from the perspective of human epilepsy and its neurobiology, based on the idea that we use models of human disorders to understand the mechanisms of the disorder that we cannot study directly in people. The logic then follows that to understand the human condition, the model ideally must have identical features. If the features are not identical, then, before one draws conclusions from the model, one must be very specific about how exactly the two states match and how they differ. Otherwise one risks the potential of drawing conclusions that may be inappropriate for the clinical situation. It is in this light that this article is written. It is highly selective in the issues discussed, and no doubt somewhat biased in its presentation. But it is based on some thought of what are some of the issues that are important in understanding human epilepsy, and then using those issues to compare reality to the model. The reader will no doubt notice the limited topics as well as the relatively sparse referencing, especially for a subject that has been researched as much as this one. There are no doubts some readers who will object significantly to some of the conclusions that are drawn, and "intense" discussions may ensue. Those objections are a good thing, because it is the ferment of scientific disagreement...

Developing cell transplantation for temporal lobe epilepsy

“…36 In contrast, kainate injection results in unilateral hippocampal cell loss and mossy fiber sprouting similar to that observed in patients with MTLE (except that CA1 pyramidal cell loss is more marked in patients with MTLE, whereas CA3 cell loss predominates in the kainate model) and produces the delayed appearance of 2 types of spontaneous epileptic seizures with electroencephalography activity similar to that seen in humans. 6 In pilocarpine-injected rats, however, the only consistent hippocampal neuron loss is in the hilus of the dentate gyrus. 49 Due to its closer relationship to the ultrastructural and electrophysiological changes in human MTLE, the kainate model may be best suited for use in transplantation experiments to test the functional ability of grafted cells for circuit modification.…”

“…36 In kindling, a series of electrically induced seizures results in an increasing seizure duration and enhanced behavioral involvement of those induced seizures until a plateau is reached. 6 Subconvulsive electrical kindling of the amygdala or tractus perforans usually leads to less significant histopathological alterations, including structural reorganization that is more similar to the epileptogenic hippocampus of patients with focal lesions than the changes seen in Ammon horn sclerosis. 36 In contrast, kainate injection results in unilateral hippocampal cell loss and mossy fiber sprouting similar to that observed in patients with MTLE (except that CA1 pyramidal cell loss is more marked in patients with MTLE, whereas CA3 cell loss predominates in the kainate model) and produces the delayed appearance of 2 types of spontaneous epileptic seizures with electroencephalography activity similar to that seen in humans.…”

Status Epilepticus and Psychosis of Epilepsy

“…4 Deep brain stimulation may cause kindling antagonism; ie, stimulation in one area can inhibit the formation of kindled seizures from another site. 5 Intermittent stimulation is less likely to cause neural tissue damage and functional disruption or habituation.…”

Models of experimental epilepsy

“…23 Sıçanlarda limbik yapıların elektrik stimülasyonu ile uyarılması ile oluşturulan kindling (tutuşturma, ateşleme) nöbetleri: TLE'nin en yaygın biçimde kullanılan modellerinden biridir. [24][25][26] Epileptojenik etkilerine ilaveten kindling;…”