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词条 Kindling model
释义

  1. Method

  2. Historical perspective

  3. New approaches

  4. See also

  5. References

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] The kindling model was first proposed in the late 1960s by Goddard and colleagues.[2] Although kindling is a widely used model, its applicability to human epilepsy is controversial.[1]

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 amount 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 neocortex was developed using optogenetics (light) instead of passing electrical current.[10]

See also

  • Kindling (sedative–hypnotic withdrawal)
  • Epileptogenesis
  • Racine Stages (a method by which seizure severity is quantified in animal models of epilepsy)

References

1. ^1 2 3 4 5 6 7 8 9 {{cite journal |author=Bertram E |title=The relevance of kindling for human epilepsy |journal=Epilepsia |volume=48 |issue=Supplement 2 |pages=65–74 |year=2007 |pmid=17571354 |doi=10.1111/j.1528-1167.2007.01068.x}}
2. ^{{cite journal |author= Sato M|title=Kindling: An experimental model of epilepsy |journal=Psychiatry and Clinical Neurosciences |volume=36 |issue=4 |pages=440–441 |year=2008 |pmid= |doi=10.1111/j.1440-1819.1982.tb03123.x |url=http://www3.interscience.wiley.com/cgi-bin/fulltext/120156204/PDFSTART |format=PDF}}
3. ^1 2 {{cite book |chapter=The kindling model of epilepsy |vauthors=Abel MS, McCandless DW |veditors=Adams RN, Baker GB, Baker JM, Bateson AN, Boisvert DP, Boulton AA |title=Neuromethods: Animal Models of Neurological Disease |publisher=Humana Press |location=Totowa, NJ |year=1992 |pages=153–155 |isbn=0-89603-211-6 |display-editors=etal}}
4. ^{{cite journal|title=The pathophysiology of post traumatic epilepsy |author1=PK Sahoo |author2=KI Mathai |author3=GV Ramdas |author4=MN Swamy |journal=Indian Journal of Neurotrauma |volume=4 |issue=1 |pages=11–14 |year=2007 |url=http://www.ijntonline.com/June07/abstracts/03.PDF |format=PDF |doi=10.1016/s0973-0508(07)80004-9 |deadurl=yes |archiveurl=https://web.archive.org/web/20101202010046/http://ijntonline.com/June07/abstracts/03.PDF |archivedate=2010-12-02 }}{{cite journal |authors=Temkin NR, Jarell AD, Anderson GD |title=Antiepileptogenic agents: how close are we? |journal=Drugs |volume=61 |issue=8 |pages=1045–55 |year=2001 |pmid=11465868 |doi=10.2165/00003495-200161080-00002}}
5. ^{{cite journal |vauthors=Morimoto K, Fahnestock M, Racine RJ |title=Kindling and status epilepticus models of epilepsy: Rewiring the brain |journal=Prog. Neurobiol. |volume=73 |issue=1 |pages=1–60 |date=May 2004 |pmid=15193778 |doi=10.1016/j.pneurobio.2004.03.009}}
6. ^1 {{cite journal |author1=McNamara JO |author2=Byrne MC |author3=Dasheiff RM |author4=JG Fitz |title=The Kindling Model of Epilepsy; a Review|journal=Progress in Neurobiology|volume=15 |issue=2 |pages=139–59 |year=1980 |pmid=6109361 |doi=10.1016/0301-0082(80)90006-4}}
7. ^{{cite journal |vauthors=Delgado JM, Sevillano M|title=Evolution of repeated hippocampal seizures in the cat|journal=Electroenceph. clin. Neurophys|volume=13 |issue=2 |pages=722–733|year=1961 |doi=10.1016/0013-4694(61)90104-3}}
8. ^{{cite journal |author=Goddard GV |title=Development of epileptic seizures through brain stimulation at low intensity|journal=Nature|volume=214 |issue=5092|pages=1020–1 |year=1967 |pmid=6055396|doi=10.1038/2141020a0 }}
9. ^{{cite journal |vauthors=Goddard GV, McIntyre DC, Leech CK |title=A permanent change in brain function resulting from daily electrical stimulation|journal=Exp Neurol|volume=25 |issue=3 |pages=295–330 |year=1969 |pmid= 4981856 |doi=10.1016/0014-4886(69)90128-9}}
10. ^{{Cite journal|last=Cela|first=Elvis|last2=McFarlan|first2=Amanda R.|last3=Chung|first3=Andrew J.|last4=Wang|first4=Taiji|last5=Chierzi|first5=Sabrina|last6=Murai|first6=Keith K.|last7=Sjöström|first7=P. Jesper|date=December 2019|title=An Optogenetic Kindling Model of Neocortical Epilepsy|url=http://www.nature.com/articles/s41598-019-41533-2|journal=Scientific Reports|volume=9|issue=1|doi=10.1038/s41598-019-41533-2|issn=2045-2322}}

3 : Neurological disorders|Neurology|Epilepsy
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