Effects of Oxcarbazepine on the Behavioral Response and Neuroanatomical Alterations Following Administration of Kainic Acid

Epilepsy is considered to be a disorder intrinsic to thebrain, deriving from either a hereditary tendency or a priorinsult, in which a portion of the brain is rendered electri-cally unstable [1].Temporal lobe epilepsy is the most devastating form ofepilepsy commonly encountered in the adult population.The attacks involve loss of consciousness, thus limitingperformance of normal functions and exposing the indi-vidual to bodily injury. Moreover, long-standing or phar-macologically intractable temporal lobe epilepsy is fre-quently associated with the loss of neurons from the hip-pocampus and other brain regions [2-4] Unfortunately,pharmacologically intractable cases are rather common,owing to the relatively low efficacy against this conditionof the available anticonvulsants.As ethical considerations rule out use of the modernneuroscientific tools in intact human brain, the study ofepilepsy has been dependent upon use of model systems.Much of what is known about the epilepsy is derived fromanimal models [5]. Basic models of epilepsy have beenused to explore questions about seizures and the electricalactivity of the brain. These questions are related to theunderlying EEG generators of electrical potentials associ-ated with seizures: the nature and identity of neuronalsystems able to produce epilepsy; issues of why seizuresstart, spread and stop, and why seizures occur when theydo; what type of pathologies in brain give rise to seizures;whether seizures cause damage to brain; and the mecha-nisms of action of anticonvulsant drugs [6-8].In past decades, a variety of animal models of epilepsyhave been used to identify and evaluate chemicals withanticonvulsant efficacy. It is of particular interest thatsystemic administration of kainic acid (KA), an analogueof the excitatory neurotransmitter glutamate, causes per-sistent seizure activity and a disseminated pattern of sei-zure-related brain damage. For reasons that are incom-pletely understood, KA has an especially prominent toxiceffect on the hippocampus, even when injected systemi-cally, or at brain sites remotes from hippocampus [9-11].The accompanying hippocampal lesions may be consid-ered to portray the pattern of limbic cell damage that canoccur with clinical status epilepticus [12,13].It is interesting that the anticonvulsant activity and sideeffects of several chemicals have been tested in animalmodels of kainite-induced epilepsy. For example, somebenzodiazepines, certain barbiturates and trimethadioneare most effective in preventing KA-induced seizures andseizure-induced brain damage [14-17], while chloral hy-drate or diethyl ether are less effective in inhibiting thebehavioral and neuropathological changes caused by KA[18]. Diphenylhydantoin, carbamazepine, valproate andethosuximide have not a clear anticonvulsive action onseizures induced by KA [19,20].On the other hand, oxcarbazepine has been extensivelytested in humans [21]. However no large comparativestudies on efficacy have been conducted, therefore the aimof this experimental work was to test the possible protec-tive action of the oxcarbazepine against the seizures andbrain damage induced by KA administration.