Alternate-site kindling in the guinea-pig results in accelerated seizure progression and generalization

Teskey, G. Campbell; Thiessen, Elizabeth J; Gilbert, Trevor H.

doi:10.1016/s0920-1211(98)00103-x

Cited by 12 publications

(9 citation statements)

References 26 publications

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“…We targeted ChR2 to primary motor cortex (M1) of male C57BL/6 J mice aged postnatal day (P) 30–45 using bilateral stereotaxic injection of AAV-CaMKIIα-hChR2-E123T/T159C-p2A-EYFP (UNC Virus Core, North Carolina, USA), since two kindling sites are known to function better than one 51 . Males were chosen solely instead of females since the estrus cycle can affect seizure susceptibility 52 .…”

Section: Methodsmentioning

confidence: 99%

An Optogenetic Kindling Model of Neocortical Epilepsy

Cela

McFarlan

Chung

et al. 2019

Sci Rep

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Epileptogenesis is the gradual process by which the healthy brain develops epilepsy. However, the neuronal circuit changes that underlie epileptogenesis are not well understood. Unfortunately, current chemically or electrically induced epilepsy models suffer from lack of cell specificity, so it is seldom known which cells were activated during epileptogenesis. We therefore sought to develop an optogenetic variant of the classical kindling model of epilepsy in which activatable cells are both genetically defined and fluorescently tagged. We briefly optogenetically activated pyramidal cells (PCs) in awake behaving mice every two days and conducted a series of experiments to validate the effectiveness of the model. Although initially inert, brief optogenetic stimuli eventually elicited seizures that increased in number and severity with additional stimulation sessions. Seizures were associated with long-lasting plasticity, but not with tissue damage or astrocyte reactivity. Once optokindled, mice retained an elevated seizure susceptibility for several weeks in the absence of additional stimulation, indicating a form of long-term sensitization. We conclude that optokindling shares many features with classical kindling, with the added benefit that the role of specific neuronal populations in epileptogenesis can be studied. Links between long-term plasticity and epilepsy can thus be elucidated.

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Section: Methodsmentioning

confidence: 99%

An Optogenetic Kindling Model of Neocortical Epilepsy

Cela

McFarlan

Chung

et al. 2019

Sci Rep

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“…Since its first descriptions over 20 years ago this phenomenon has been examined for the potential underlying mechanisms as the observation is almost counterintuitive, that seizures from one site would suppress seizures from another. Some factors have become clear: norepinephrine can play a role in modulating antagonism, that antagonism is protocol and site specific and that it may not occur in all species (Applegate et al, 1986; Teskey et al, 1999; Kogure et al, 2000; Matsuda et al, 2003). Does the observation have relevance for human epilepsy?…”

Section: Kindling To Spontaneous Seizuresmentioning

confidence: 99%

The Relevance of Kindling for Human Epilepsy

2007

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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...

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“…Although most kindling investigations have utilized rats, kindling has been described in many other animals, including amphibians, reptiles, mice, gerbils, cats, monkeys, baboons [21], and guinea-pigs [3,4,22,23]. It would be surprising to find a phenomenon that bridges vertebrates, including amphibians, reptiles, and mammals that would not include humans.…”

Section: Kindling As a Model Of Brain Plasticitymentioning

confidence: 99%

“…With repeated stimulation, guinea-pigs show some initial growth of the electrographic indices and behavioural seizures. However, unlike rats, guinea-pigs become arrested at partial and complex partial seizures and do not progress to fully generalized convulsions during regular single-site kindling [22,23]. This suggests that guinea-pig kindling may be a better model for human complex partial epilepsy because the majority of humans with complex partial epilepsy also do not progress to fully generalized convulsions.…”

Section: The Amygdala -A Discrete Multitasking Manager 290mentioning

confidence: 99%

Amygdalar Models of Neurological and Neuropsychiatric Disorders

Gilbert¹

2012

The Amygdala - A Discrete Multitasking Manager

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Alternate-site kindling in the guinea-pig results in accelerated seizure progression and generalization

Cited by 12 publications

References 26 publications

An Optogenetic Kindling Model of Neocortical Epilepsy

An Optogenetic Kindling Model of Neocortical Epilepsy

The Relevance of Kindling for Human Epilepsy

Amygdalar Models of Neurological and Neuropsychiatric Disorders

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