Kindling model

Last updated

Kindling is a commonly used model for the development of seizures and epilepsy in which the duration and behavioral involvement of induced seizures increases after seizures are induced repeatedly. [1] Kindling is also referred as an animal visual model of epilepsy that can be produced by focal electrical stimulation in the brain. This is mainly used in visualising epilepsy in humans. The kindling model was first proposed in the late 1960s by Graham V. Goddard and colleagues. [2] Although kindling is a widely used model, its applicability to human epilepsy is controversial. [1]

Contents

Method

The word kindling is a metaphor: the increase in response to small stimuli is similar to the way small burning twigs can produce a large fire. [3] It is used by scientists to study the effects of repeated seizures on the brain. [1] A seizure may increase the likelihood that more seizures will occur; an old saying in epilepsy research is "seizures beget seizures". [1] Repeated stimulation "lowers the threshold" for more seizures to occur. [4]

The brains of experimental animals are repeatedly stimulated, usually with electricity, to induce the seizures. [1] Chemicals may also be used to induce seizures. [3] The seizure that occurs after the first such electrical stimulation lasts a short time and is accompanied by a small amount of behavioral effects compared with seizures that result from repeated stimulations. [1] With further seizures, the accompanying behavior intensifies, for example progressing from freezing in early stimulations to convulsions in later ones. [5] The lengthening of duration and intensification of behavioral accompaniment eventually reaches a plateau after repeated stimulation. [1] Even if animals are left unstimulated for as long as 12 weeks, the effect remains; the response to stimulation remains higher than it had been before. [3]

It has been reported that repeated seizure stimulation can result in spontaneous seizures, but studies have had conflicting findings on this question. [1] In humans, some seizure disorders come to an end by themselves even after large numbers of seizures. [1] However, in both human epilepsy and in some animal models, evidence suggests that a process like that found in kindling does occur. [1]

Historical perspective

Already in the 1950s and 1960s, numerous authors recognized the seizure-inducing potential of focal stimulation. [6] Here, Delgado and Sevillano demonstrated that repeated low-intensity stimuli to the hippocampus could lead to progressive increase of electrically evoked seizure activity. [7] Yet, it was not until the late 1960s that Graham Goddard recognized the potential importance of this phenomenon and coined the term 'kindling'. [8] Further research by Goddard on the characteristics of the kindling phenomenon led to his conclusion that kindling can be used to model human epileptogenesis, learning and memory. [9] The publication of these results opened a completely new niche for epilepsy research and has stimulated a significant number of studies on the subject of kindling and its relevance to human epilepsy. [6]

New approaches

In 2019, a new model to develop kindling in the neocortex was developed using optogenetics (light) instead of passing electrical current. [10] In 2021, "optokindling" by activating pyramidal cells in the piriform cortex has shown to disrupt the GABA production of feedback inhibitory cells, which led to the progression of seizure severity in mice. [11]

See also

Related Research Articles

A gamma wave or gamma rhythm is a pattern of neural oscillation in humans with a frequency between 25 and 140 Hz, the 40 Hz point being of particular interest. Gamma rhythms are correlated with large scale brain network activity and cognitive phenomena such as working memory, attention, and perceptual grouping, and can be increased in amplitude via meditation or neurostimulation. Altered gamma activity has been observed in many mood and cognitive disorders such as Alzheimer's disease, epilepsy, and schizophrenia. Elevated gamma activity has also been observed in moments preceding death.

<span class="mw-page-title-main">Vagus nerve stimulation</span> Medical treatment that involves delivering electrical impulses to the vagus nerve.

Vagus nerve stimulation (VNS) is a medical treatment that involves delivering electrical impulses to the vagus nerve. It is used as an add-on treatment for certain types of intractable epilepsy and treatment-resistant depression.

Long-term or "continuous" video-electroencephalography (EEG) monitoring is a diagnostic technique commonly used in patients with epilepsy. It involves the long-term hospitalization of the patient, typically for days or weeks, during which brain waves are recorded via EEG and physical actions are continuously monitored by video. In epileptic patients, this technique is typically used to capture brain activity during seizures. The information gathered can be used for initial prognosis or long-term care management.

<span class="mw-page-title-main">Kainic acid</span> Chemical compound

Kainic acid, or kainate, is an acid that naturally occurs in some seaweed. Kainic acid is a potent neuroexcitatory amino acid agonist that acts by activating receptors for glutamate, the principal excitatory neurotransmitter in the central nervous system. Glutamate is produced by the cell's metabolic processes and there are four major classifications of glutamate receptors: NMDA receptors, AMPA receptors, kainate receptors, and the metabotropic glutamate receptors. Kainic acid is an agonist for kainate receptors, a type of ionotropic glutamate receptor. Kainate receptors likely control a sodium channel that produces excitatory postsynaptic potentials (EPSPs) when glutamate binds.

Sensitization is a non-associative learning process in which repeated administration of a stimulus results in the progressive amplification of a response. Sensitization often is characterized by an enhancement of response to a whole class of stimuli in addition to the one that is repeated. For example, repetition of a painful stimulus may make one more responsive to a loud noise.

<span class="mw-page-title-main">Temporal lobe epilepsy</span> Chronic focal seizure disorder

In the field of neurology, temporal lobe epilepsy is an enduring brain disorder that causes unprovoked seizures from the temporal lobe. Temporal lobe epilepsy is the most common type of focal onset epilepsy among adults. Seizure symptoms and behavior distinguish seizures arising from the medial temporal lobe from seizures arising from the lateral (neocortical) temporal lobe. Memory and psychiatric comorbidities may occur. Diagnosis relies on electroencephalographic (EEG) and neuroimaging studies. Anticonvulsant medications, epilepsy surgery and dietary treatments may improve seizure control.

Reflex seizures are epileptic seizures that are consistently induced by a specific stimulus or trigger making them distinct from other epileptic seizures, which are usually unprovoked. Reflex seizures are otherwise similar to unprovoked seizures and may be focal, generalized, myoclonic, or absence seizures. Epilepsy syndromes characterized by repeated reflex seizures are known as reflex epilepsies. Photosensitive seizures are often myoclonic, absence, or focal seizures in the occipital lobe, while musicogenic seizures are associated with focal seizures in the temporal lobe.

The postictal state is the altered state of consciousness after an epileptic seizure. It usually lasts between 5 and 30 minutes, but sometimes longer in the case of larger or more severe seizures, and is characterized by drowsiness, confusion, nausea, hypertension, headache or migraine, and other disorienting symptoms.

Racine stages are a categorization of epileptic seizures proposed by Ronald J. Racine in 1972. Prior to Racine's research in epilepsy, a quantifiable means to describe seizure intensities and their causes was not readily available. Racine's work allowed for epilepsy to be understood on a level previously thought impossible.

Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individual cells, light-activated enzymes and transcription factors allow precise control of biochemical signaling pathways. In systems neuroscience, the ability to control the activity of a genetically defined set of neurons has been used to understand their contribution to decision making, learning, fear memory, mating, addiction, feeding, and locomotion. In a first medical application of optogenetic technology, vision was partially restored in a blind patient.

Post-traumatic epilepsy (PTE) is a form of acquired epilepsy that results from brain damage caused by physical trauma to the brain. A person with PTE experiences repeated post-traumatic seizures more than a week after the initial injury. PTE is estimated to constitute 5% of all cases of epilepsy and over 20% of cases of acquired epilepsy.

Epileptogenesis is the gradual process by which a typical brain develops epilepsy. Epilepsy is a chronic condition in which seizures occur. These changes to the brain occasionally cause neurons to fire in an abnormal, hypersynchronous manner, known as a seizure.

<span class="mw-page-title-main">Ganaxolone</span> Chemical compound

Ganaxolone, sold under the brand name Ztalmy, is a medication used to treat seizures in people with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD). Ganaxolone is a neuroactive steroid gamma-aminobutyric acid (GABA) A receptor positive modulator.

Kindling due to substance withdrawal refers to the neurological condition which results from repeated withdrawal episodes from sedative–hypnotic drugs such as alcohol and benzodiazepines.

Forced Normalization (FN) is a psychiatric phenomenon in which a long term episodic epilepsy or migraine disorder is treated, and, although the electroencephalogram (EEG) appears to have stabilized, acute behavioral, mood, and psychological disturbances begin to manifest. If, or when, treatment for the disorder is halted, the disturbances go away, but the episodic spikes on the EEG reappear. H. Landolt coined the term 'Forced Normalization' in 1953 in response to a change he witnessed in epileptic EEGs, which monitor electrical activity in the brain. These changes were followed by abrupt behavioral changes in the patient. Landolt concluded that forced normalization is "the phenomenon characterized by the fact that, with the occurrence of psychotic states, the electroencephalography becomes more normal or entirely normal, as compared with previous and subsequent EEG findings." Forced normalization, as described by Landolt, was therefore an electrophysiological phenomenon with the electroencephalograph at its helm.

Animal models of epilepsy have helped to advance the understanding of how normal brains develop epilepsy, and have been used in pre-clinical trials of antiepileptic drugs. Epilepsy is a set of syndromes which have in common a predisposition to recurrent epileptic seizures. Animal models of epilepsy and seizures can be divided into three basic categories: genetic animal models, chemically induced models, and electrically induced models. New models are using light-gated ion channels to turn on cell firing and these are part of optogenetic induction models of epilepsy.

Granule cell dispersion is one of the abnormal structural changes that has been shown in brains of patients with temporal lobe epilepsy. It has also been shown in different animal models, such as the kainic acid model, pilocarpine model, and kindling model. But granule cell dispersion was not found by using perforant pathway stimulation.

Gene therapy is being studied for some forms of epilepsy. It relies on viral or non-viral vectors to deliver DNA or RNA to target brain areas where seizures arise, in order to prevent the development of epilepsy or to reduce the frequency and/or severity of seizures. Gene therapy has delivered promising results in early stage clinical trials for other neurological disorders such as Parkinson's disease, raising the hope that it will become a treatment for intractable epilepsy.

Chemogenetics is the process by which macromolecules can be engineered to interact with previously unrecognized small molecules. Chemogenetics as a term was originally coined to describe the observed effects of mutations on chalcone isomerase activity on substrate specificities in the flowers of Dianthus caryophyllus. This method is very similar to optogenetics; however, it uses chemically engineered molecules and ligands instead of light and light-sensitive channels known as opsins.

Musicogenic seizure, also known as music-induced seizure, is a rare type of seizure, with an estimated prevalence of 1 in 10,000,000 individuals, that arises from disorganized or abnormal brain electrical activity when a person hears or is exposed to a specific type of sound or musical stimuli. There are challenges when diagnosing a music-induced seizure due to the broad scope of triggers, and time delay between a stimulus and seizure. In addition, the causes of musicogenic seizures are not well-established as solely limited cases and research have been discovered and conducted respectively. Nevertheless, the current understanding of the mechanism behind musicogenic seizure is that music triggers the part of the brain that is responsible for evoking an emotion associated with that music. Dysfunction in this system leads to an abnormal release of dopamine, eventually inducing seizure.

References

  1. 1 2 3 4 5 6 7 8 9 10 Bertram E (2007). "The relevance of kindling for human epilepsy". Epilepsia. 48 (Supplement 2): 65–74. doi: 10.1111/j.1528-1167.2007.01068.x . PMID   17571354.
  2. ↑ Sato M (2008). "Kindling: An experimental model of epilepsy" (PDF). Psychiatry and Clinical Neurosciences. 36 (4): 440–441. doi:10.1111/j.1440-1819.1982.tb03123.x. S2CID   146513524.[ permanent dead link ]
  3. 1 2 3 Abel MS, McCandless DW (1992). "The kindling model of epilepsy". In Adams RN, Baker GB, Baker JM, Bateson AN, Boisvert DP, Boulton AA, et al. (eds.). Neuromethods: Animal Models of Neurological Disease. Totowa, NJ: Humana Press. pp. 153–155. ISBN   0-89603-211-6.
  4. ↑ PK Sahoo; KI Mathai; GV Ramdas; MN Swamy (2007). "The pathophysiology of post traumatic epilepsy" (PDF). Indian Journal of Neurotrauma. 4 (1): 11–14. doi:10.1016/s0973-0508(07)80004-9. S2CID   144797725. Archived from the original (PDF) on 2010-12-02. Temkin NR, Jarell AD, Anderson GD (2001). "Antiepileptogenic agents: how close are we?". Drugs. 61 (8): 1045–55. doi:10.2165/00003495-200161080-00002. PMID   11465868. S2CID   46964062.
  5. ↑ Morimoto K, Fahnestock M, Racine RJ (May 2004). "Kindling and status epilepticus models of epilepsy: Rewiring the brain". Prog. Neurobiol. 73 (1): 1–60. doi:10.1016/j.pneurobio.2004.03.009. PMID   15193778. S2CID   36849482.
  6. 1 2 McNamara JO; Byrne MC; Dasheiff RM; JG Fitz (1980). "The Kindling Model of Epilepsy; a Review". Progress in Neurobiology. 15 (2): 139–59. doi:10.1016/0301-0082(80)90006-4. PMID   6109361. S2CID   2843956.
  7. ↑ Delgado JM, Sevillano M (1961). "Evolution of repeated hippocampal seizures in the cat". Electroenceph. Clin. Neurophys. 13 (2): 722–733. doi:10.1016/0013-4694(61)90104-3.
  8. ↑ Goddard GV (1967). "Development of epileptic seizures through brain stimulation at low intensity". Nature. 214 (5092): 1020–1. Bibcode:1967Natur.214.1020G. doi:10.1038/2141020a0. PMID   6055396. S2CID   2203065.
  9. ↑ Goddard GV, McIntyre DC, Leech CK (1969). "A permanent change in brain function resulting from daily electrical stimulation". Exp Neurol. 25 (3): 295–330. doi:10.1016/0014-4886(69)90128-9. PMID   4981856.
  10. ↑ Cela, Elvis; McFarlan, Amanda R.; Chung, Andrew J.; Wang, Taiji; Chierzi, Sabrina; Murai, Keith K.; Sjöström, P. Jesper (December 2019). "An Optogenetic Kindling Model of Neocortical Epilepsy". Scientific Reports. 9 (1): 5236. Bibcode:2019NatSR...9.5236C. doi:10.1038/s41598-019-41533-2. ISSN   2045-2322. PMC   6437216 . PMID   30918286.
  11. ↑ Ryu, Brendan; Nagappan, Shivathmihai; Santos-Valencia, Fernando; Lee, Psyche; Rodriguez, Erica; Lackie, Meredith; Takatoh, Jun; Franks, Kevin M. (April 2021). "Chronic loss of inhibition in piriform cortex following brief, daily optogenetic stimulation". Cell Reports. 35 (3): 109001. doi: 10.1016/j.celrep.2021.109001 . ISSN   2211-1247. PMC   8102022 . PMID   33882304.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.