Epilepsy kindling model

McNamara JO, Bonhaus DW, Crain BJ, Gellman RJ, Shin C (1987) Biochemical and pharmacological studies of neurotransmitters in the kindling model. In Neurotransmitters and epilepsy. Jobe PC and Laird HE (Eds) Clifton, NJ, Humana 115-160... 

Loscher, W. (1998) Pharmacology of glutamate receptor antagonists in the kindling model of epilepsy. Prog Neurohiol 54 721-741. 

Whereas the genetic and kindling models have been widely used to investigate possible neurotransmitter defects that cause different types of epilepsy, rodent models in which seizures are induced by electroshock, or by convulsant drugs such as pentylenetetrazol (also called pentetrazol, leptazol), picrotoxin or bicuculline, are mainly used in screening procedures to identify potential anticonvulsants. 

Mode of action. Initially the experimental studies were undertaken on the racemic mixture which contained the R- and the S-enantiomers of etiracetam. Only the S-enantiomer was shown to have antiepileptic potential in a wide range of animal models of epilepsy. It was shown to be particularly active in the kindling models but the precise action of this drug at the cellular level is uncertain. 

Evaluation of oc2A-ARD79N/D79Nmice in the kindling model of epilepsy revealed that these animals exhibited increased epileptogenesis coupled with an enhanced... 

ChenLS,WeingartJB, McNamaraJO. Biochemical andradiohistochemical analyses of a2 adrenergic receptors in the kindling model of epilepsy. J Pharmacol Exp Ther 1990 253 1272-1277. 

Wang, Y. et al. (2003) A kindling model of pharmacoresistant temporal lobe epilepsy in Sprague-Dawley rats induced by Coriaria lactone and its possible mechanism. Epilepsia, 44 (4), 475-488. 

Loscher W, Honack D, Rundfeldt C. Antiepileptogenic effects of the novel anticonvulsant levetiracetam (ucb L059) in the kindling model of temporal lobe epilepsy. J Pharm Exp Ther 1998 284 474 79. 

Kamphuis, W. and Lopes da Silva, F. H. (1990) The kindling model of epilepsy the role of GABAergic inhibition. Neurosci. Res. Comm. 6,1-10. 

The definition of an antiepileptogenic compound is one that prevents or slows the process of developing epilepsy (Cole and Dichter, 2002). Several experimental studies have aimed at preventing epileptogenesis in animal models, including SE and kindling models, by administering AEDs. Some have mild or questionable effects, and others are without effect even if they neuroprotect (Walker et al., 2002). 

Adams, B, Sazgar, M, Osehobo, P, Van der Zee, CE, Diamond, J, Fahnestock, M, Racine, RJ (1997) Nerve growth factor accelerates seizure development, enhances mossy fiber sprouting, and attenuates seizure-induced decreases in neuronal density in the kindling model of epilepsy. J Neurosci, 17 5288-5296. 

McNamara, JO, Bonhaus, W, Shin, C. The kindling model of epdepsy In Schwartzkroin PA, editor. Epilepsy models, mechanisms, and concepts. Cambridge Cambridge University Press, 1993 21 7... 

Figure 5. Cross-sectional microscope images (20X) of hypothesized PpIX fluorescence in rat hippocampus. When compared to control (A), the seizure focus (B) in a rat kindling model of epilepsy shows a dramatic increase in fluorescence at 635 nm using 400 nm excitation light.

Morimoto K, Fahnestock M, Racine RJ. Kindling and status epilepticus models of epilepsy rewiring the brain. Prog Neurobiol. 2004 73 1-60. 

Moraes ME, Galvis-Alonso OY, Garcia-Cairasco N. Audiogenic kindling in the Wistar rat a potential model for recruitment of limbic structures. Epilepsy Research 2000 39 251-259. 

Yehuda and co-workers were the first to demonstrate that PUFAs can have an anticonvulsant effect in vivo (Yehuda, Carasso Mostofsky, 1994). They administered a mixture of a-linolenic/linoleic acid in a ratio of 1 4 to rats for 3 wk and assessed the protection against acute convulsant doses of pentylenetetrazole (PTZ), repeated subconvulsive doses of PTZ (chemical kindling), in rats made epileptic by a TeCI, injection in the amygdala and in rats made seizure-prone to acoustic stimulation by repeated injection with p-cresol. In all epilepsy models, the treatment either prevented the occurrence of seizures or increased the threshold for convulsions and diminished the severity and duration. 

Mathem G, Bertram E, Babb T, Pretorius J, Kuhlman P, Spradlin S, et al. In contrast to kindled seizures, the frequency of spontaneous epilepsy in the limbic stains model correlates with greater aberrant fascia dentata excitatory and inhibitory axon sprouting, and increased staining forN-methyl-D aspartate, AMPA and GABA-A receptors. Neuroscience 1997 77 1003-1019. 

It is a misconception, however, that all plants used for the treatment of epilepsy in folk medicine are safe to use and that their use is rational. A number of highly addictive and toxic compounds have been isolated from these plants including LSD, A8 and A9 tetrahydrocannabinols, cannabidiol and cocaine. A8 and A9 tertrahydrocannabinols have anticonvulsant activity in various experimental models of epilepsy including kindling... 

Since the methods of modeling epilepsy are so diverse, it is imperative to select the most appropriate models for studying epileptogenesis. The most common methods of studying this process are in rodents (Table 6.1), in particular the kindling or post-SE models. 

Treatment during or after brain injury in chronic epilepsy models, such as SE and kindling, reduce cell loss and neuronal death. Such neuroprotection could contribute to modification of or delay in the development of epilepsy. 

Loscher, W (2002) Animal models of epilepsy for the development of antiepUeptogenic and disease-modifying drugs. A comparison of the pharmacology of kindling and post-status epi-lepticus models of temporal lobe epilepsy. Epilepsy Res, 50 105—123. 

Models for partial epilepsy employ intracerebral tetanus toxin and kindling (repetitive, initially subconvulsive electrical or chemical stimulation to a focal target, resulting in repetitive seizures). 

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